环磷酰胺辅助化疗对不同年龄乳腺癌患者卵巢功能的损伤情况及机制研究

目的:以月经变化情况及血清激素水平为观察指标,探讨环磷酰胺辅助化疗方案对绝经前不同年龄段乳腺癌患者卵巢功能的损伤情况及可能的机制研究。方法:收集2017年1月至2018年12月期间在我院接受环磷酰胺辅助化疗的绝经前乳腺癌患者77例。患者年龄范围为26-48岁,并按年龄分为两组:≤35岁组为16例;>35岁组为61例。调查研究两组患者化疗前后的月经情况,以及血清激素水平(E、FSH、AMH)。同时进行动物实验,采用单剂量环磷酰胺(200 mg/kg)处理不同月龄组(3月龄和6月龄)雌性C57BL/6J小鼠,每组小鼠12例。在环磷酰胺处理前及处理后一周,检测小鼠血清AMH水平,计数小鼠卵巢卵泡数量。结果:环磷酰胺化疗后,>35岁组与≤35岁组间比较,>35岁组闭经率更高,复经率更低,血清AMH和E2水平下降幅度更大(P<0.05),FSH水平升高幅度也大于≤35岁组,但差异无明显统计学意义(P>0.05)。不同年龄组内比较,≤35岁组患者化疗后的血清AMH和E2下降水平无明显差异(P>0.05);血清FSH水平明显升高(P<0.05)。而>35岁组的患者化疗后,血清AMH和E2水平明显下降,FSH水平明显升高,差异均有统计学意义(P<0.05)。不同月龄组小鼠环磷酰胺处理前后,血清AMH水平明显下降,卵巢原始卵泡和生长卵泡数明显较少,差异均有统计学意义(P<0.05),且6月龄组小鼠下降程度更明显(P<0.05)。结论:环磷酰胺辅助化疗方案明显损伤患者卵巢功能,且对年龄越大者损伤程度越严重,更易导致不可逆性卵巢损伤。     

Within-laboratory and between-laboratory variability in the measurement of anti-müllerian hormone determined within an external quality assurance scheme

Ten laboratories in an external quality assurance scheme used the same assay to measure anti-müllerian hormone concentration (Beckman Coulter Gen II) and received twenty serum samples distributed over a 15 month period. The mean bias for all results was only ?0.089%, but there was large coefficient of repeatability of 38.8% (sample bias ranged from ?37.9% to +54.7%). While each laboratory showed good reproducibility, there was a wide range of average values relative to the consensus value from ?24.0% to +22.7%. This between-laboratory variability suggests clinicians should use the same laboratory to avoid problems with result interpretation.     

High levels of Paleolithic Y-chromosome lineages characterize Serbia

Whether present-day European genetic variation and its distribution patterns can be attributed primarily to the initial peopling of Europe by anatomically modern humans during the Paleolithic, or to latter Near Eastern Neolithic input is still the subject of debate. Southeastern Europe has been a crossroads for several cultures since Paleolithic times and the Balkans, specifically, would have been part of the route used by Neolithic farmers to enter Europe. Given its geographic location in the heart of the Balkan Peninsula at the intersection of Central and Southeastern Europe, Serbia represents a key geographical location that may provide insight to elucidate the interactions between indigenous Paleolithic people and agricultural colonists from the Fertile Crescent. In this study, we examine, for the first time, the Y-chromosome constitution of the general Serbian population. A total of 103 individuals were sampled and their DNA analyzed for 104 Y-chromosome bi-allelic markers and 17 associated STR loci. Our results indicate that approximately 58% of Serbian Y-chromosomes (I1-M253, I2a-P37.2 and R1a1a-M198) belong to lineages believed to be pre-Neolithic. On the other hand, the signature of putative Near Eastern Neolithic lineages, including E1b1b1a1-M78, G2a-P15, J1-M267, J2-M172 and R1b1a2-M269 accounts for 39% of the Y-chromosome. Haplogroup frequency distributions in Western and Eastern Europe reveal a spotted landscape of paleolithic Y chromosomes, undermining continental-wide generalizations. Furthermore, an examination of the distribution of Y-chromosome filiations in Europe indicates extreme levels of Paleolithic lineages in a region encompassing Serbia, Bosnia-Herzegovina and Croatia, possibly the result of Neolithic migrations encroaching on Paleolithic populations against the Adriatic Sea.     

Mutational screening of SF1 and WNT4 in Tunisian women with premature ovarian failure

Background

WNT4 and SF1 genes play an important role in ovarian development. They constitute coherent candidate genes associated with premature ovarian failure (POF) pathogenesis.

Methods

We sequenced the coding region of WNT4 and SF1 in 55 Tunisian women with POF and 100 healthy controls.

Results

We identified a synonymous variation in WNT4 (c.99G>A, p.Ser33Ser) and a substitution (c.G437C) in SF1 gene inducing G146 to Ala (GGG–GCG) missense mutation. WNT4 (c.99G>A, p.Ser33Ser) was not associated with POF pathology. However, a positive association of SF1 Gly146Ala polymorphism was noted. Gly146Ala minor allele frequency was significantly higher (p = 0.029) in POF patients versus controls and Ala allele containing genotypes (p = 0.005) were positively associated with POF pathology. The carriage of 146Ala allele was also associated with a significant reduction in estradiol plasma levels.

Conclusions

SF1 Gly146Ala polymorphism seems to be associated with POF pathology in the Tunisian population likely by reducing estradiol levels.     

不同年龄大鼠血清抗中肾旁管激素水平与卵巢储备功能的关系

目的探讨不同年龄组雌性大鼠血清抗中肾旁管激素（AMH）变化的规律和原因,探讨AMH在预测卵巢储备功能方面的作用。方法SD雌性大鼠分为幼年组、成年组和老年组。运用ELISA和免疫荧光化学方法,检测血清和卵巢中AMH的表达。结果血清AMH水平,幼年组5.26±0.13 ng/mL,成年组2.34±0.11 ng/mL,老年组0.69±0.04 ng/mL,随年龄增长显著降低（P〈0.001）。卵巢中AMH阳性卵泡的数量,幼年组19.5±1.3,成年组10.8±1.5,老年组3.8±0.6,随年龄增长显著降低（P〈0.001）。结论随着大鼠年龄增长,卵巢中分泌AMH的生长卵泡数量减少,使血清AMH水平下降,提示卵巢储备功能下降。AMH是一个较好的检测卵巢储备功能的指标。     

The reproductive endocrinology of the menopausal transition

The menopause transition is a dynamic process that begins with the first appearance of menstrual irregularity and ends with a woman's final menstrual period. As ovarian follicle numbers dwindle, the hypothalamic-pituitary-ovarian axis enters a state of compensated failure. In this state, elevated FSH is capable of maintaining relatively regular folliculogenesis and ovulation, but fertility is reduced. Eventually, this state of compensated failure cannot be sustained, and the ovary becomes unable to produce functioning follicles. Recent multicenter studies from several countries have addressed the pattern of change in hormones and a model form reproductive aging has been developed that helps explain the changes in hormone patterns and fertility that accompany menopause. Perhaps more important, the hormonal changes of the menopausal transition may be predictive of future disease risk. This review will undertake an explanation of the current literature on this topic.     

桂枝茯苓胶囊对卵巢囊肿患者囊肿核摘除术后血清雌激素、AMH及LSA水平的影响

目的:探究桂枝茯苓胶囊对卵巢囊肿患者囊肿核摘除术后血清雌激素、抗苗勒氏管激素(AMH)及脂质结合唾液酸(LSA)水平的影响。方法:选择我院收治的已行囊肿核摘除术的卵巢囊肿患者39例,将其随机分为实验组及对照组。对照组18例予甲硝唑联合青霉素注射治疗;实验组21例予桂枝茯苓胶囊治疗。治疗后,对比两组的临床疗效及治疗前后血清雌激素、AMH及LSA的水平。结果:治疗后,实验组总有效率(95.2%)显著高于对照组(72.2%),差异具有统计学意义(P0.05);治疗后,两组血清雌激素、AMH水平均明显升高,血清LSA水平显著降低,差异均具有统计学意义(P0.05);与对照组比较,实验组治疗后血清雌激素、AMH较高,而LSA水平较低,差异具有统计学意义(P0.05)。结论:桂枝茯苓胶囊可以有效提高行囊肿核摘除术卵巢囊肿患者的临床疗效,这可能与其提高血清雌激素及AMH水平并降低血清LSA水平有关。     

血清25(OH)D、AMH和INHB联合检测在卵巢储备功能低下患者体外受精-胚胎移植妊娠结局中的应用价值

摘要 目的：血清25-羟维生素D[25(OH)D]、抗苗勒管激素（AMH）和抑制素B（INHB）联合检测在卵巢储备功能低下（DOR）患者体外受精-胚胎移植（IVR-ET）妊娠结局中的应用价值。方法：选择2019年8月~2021年10月我院行IVR-ET助孕的DOR患者292例,根据助孕后的妊娠结局分为妊娠组（n=158）和未妊娠组（n=134）,比较两组临床资料及血清25(OH)D、AMH和INHB水平,应用受试者工作特征（ROC）曲线评价血清25(OH)D、AMH和INHB单独及联合检测对妊娠失败的预测价值。应用单因素、多因素Logisitic回归分析妊娠失败的影响因素。结果：妊娠组血清25(OH)D、AMH、INHB水平显著高于未妊娠组（P<0.05）。ROC曲线分析显示,血清25(OH)D、AMH、INHB及三者联合检验对DOR患者IVR-ET妊娠失败的预测的曲线下面积（AUC）分别为0.714（0.631~0.802）、0.801（0.731~0.852）、0.634（0.578~0.741）、0.853（0.806~0.913）,三者联合检验对DOR患者IVR-ET妊娠失败预测AUC高于单独检验。单因素分析显示未妊娠组窦卵泡个数<5、获卵个数<8、卵泡刺激素（FSH）/黄体生成激素(LH)≥1.8、血清25(OH)D≤25.05 μg/L、血清AMH≤1.08 ng/mL、血清INHB≤84.28 pg/mL比例显著高于妊娠组（P<0.05）。多因素Logistic回归分析显示FSH/LH≥1.8、血清25(OH)D≤25.05 μg/L、血清AMH≤1.08 ng/mL、血清INHB≤84.28 pg/mL是DOR患者IVR-ET妊娠失败的危险因素（P＜0.05）。结论：血清25(OH)D、AMH和INHB 水平较低与DOR患者IVR-ET妊娠失败有关,且联合检测上述指标水平对患者IVR-ET妊娠失败有较高的辅助预测价值。     

Induced fit, folding, and recognition of the NF-kappaB-nuclear localization signals by IkappaBalpha and IkappaBbeta

Protein structure prediction codes based on the associative memory Hamiltonian were used to probe the binding modes between the nuclear localization signal (NLS) polypeptide of NF-kappaB and the inhibitors IkappaBalpha and IkappaBbeta. Experimentally, it is known that the NLS polypeptide is unstructured in the NF-kappaB complex with DNA but it forms an extended helical structure with the NLS (residues 301-304) between the two helices in the NF-kappaB/IkappaBalpha complex. The simulations included the NF-kappaB(p65) and (p50) NLS polypeptides and various mutants alone and in the presence of IkappaBalpha and IkappaBbeta. The simulations predict that the NLS polypeptide by itself binds tightly to IkappaBalpha and IkappaBbeta. In the NF-kappaB (p50/p65) heterodimer, the p50 NLS is predicted to remain free to bind to importin alpha. In the interaction with IkappaBalpha, both p65 NLSs are predicted to be bound. In IkappaBbeta, the NLS polypeptide binds to two binding sites, as seen in the crystal structure, with one site heavily favored for stable binding.