A novel loss of function mutation in exon 10 of the FSH receptor gene causing hypergonadotrophic hypogonadism: clinical and molecular characteristics

BACKGROUND: Inactivating mutations of the FSH receptor (FSHR) are a rare cause of hypergonadotrophic hypogonadism in women. Only one patient with primary amenorrhoea due to an FSHR gene mutation has been reported outside of Finland, where the prevalence of Ala189Val mutations is particularly high. METHODS AND RESULTS: Here, we describe the clinical, molecular genetic and functional characteristics associated with a novel inactivating mutation in exon 10 of the FSHR gene identified in a patient who presented with primary amenorrhoea at 17 years of age. The C to G transversion found at nucleotide 1043 causes a Pro348Arg substitution in the extracellular region of the FSHR and results in a mutant FSHR that is completely inactive in functional studies and that does not bind FSH. The proband exhibits apparent homozygosity for this recessive mutation. Her father is heterozygous for the mutation while analysis of exon 10 of the FSHR gene from her mother revealed only wild-type sequence. Chromosome painting was used to exclude deletions or rearrangements of 2p, and microsatellite markers did not show paternal uniparental isodisomy for this region. These findings suggest that the proband is hemizygous, with an inherited or de-novo microdeletion, or alternatively a de-novo gene conversion, of the accompanying FSHR allele. CONCLUSIONS: This case confirms the importance of the FSHR in female pubertal development and reproduction, and supports a relationship between phenotype and function for FSHR mutations.     

Total energy expenditure of elite synchronized swimmers measured by the doubly labeled water method

To determine the daily energy requirement of elite synchronized swimmers during moderate-intensity training, the average daily energy expenditure measured by the doubly labeled water method, was calculated for nine female Japanese national team synchronized swimmers [four senior; mean (SD) 22.5 (1.0) years old, 52.2 (3.6) kg, and five junior; 17.6 (1.1) years old, 52.8 (2.3) kg]. Their total energy expenditure (TEE) was 11.5 (2.8) MJ · day⁻¹ [2738 (672) kcal · day⁻¹]. When compared with estimated energy requirements derived from “Recommended Dietary Allowances for the Japanese”, 12.1 (0.6) MJ · day⁻¹ [2897 (139) kcal · day⁻¹], there was no difference between mean actual and estimated energy requirements. However, there were considerable differences observed on an individual basis. Their energy intake, estimated from 7- day self-reported dietary records, was 8.9 (1.7) MJ · day⁻¹ [2128 (395) kcal · day⁻¹], which was significantly lower than their TEE (P < 0.05). Resting energy expenditure (REE), as determined by indirect calorimetry, was 5.2 (0.3) MJ · day⁻¹ [1247 (75) kcal · day⁻¹]. Their physical activity level (TEE/REE) was 2.18 (0.43). These results demonstrate that the TEE values of elite female synchronized swimmers are not dissimilar to those reported for athletes participating in other sports, especially competitive swimmers during moderate-intensity training. Accepted: 26 May 2000     

高雌激素血症对雌性心肌梗塞大鼠心肌舒缩性能的影响

本文研究了高雌激素血症对雌性心肌梗塞(MI)大鼠心肌舒缩性能的影响。结果:(1)MI组血浆雌二醇(E_2)先略升高而后降低,雌二醇处理MI组(MIE_2)血浆雌二醇明显升高。(2)MIE_2组心肌纤维直径比对照假手术组(CS)及MI组显著增大(10.65±0.59 VS 7.65±0.40及10.15±0.54gm,P<0.001,<0.02)。(3)两MI组的LVSP、±dp/dt max均显著降低,T-值明显延长,尤以MIE_2组更为显著(10.5±4.1 VS 6.2±4.6ms,P<0.02)。(4)两MI组动脉压显著降低,HR减慢,LVET延长;在9天观测点,MIE_2组的HR仍较MI组显著减慢、LVET明显延长。提示高雌激素血症可使雌性心肌梗塞大鼠心肌舒缩性能降低。     

Behavioral and neurochemical effects induced by subchronic combined exposure to toluene at 40 ppm and noise at 80 dB-A in rats

We investigated whether exposure to noise, in addition to its well-known potentiating effect on toluene-induced ototoxicity, may also exacerbate behavioral disturbances and brain neurochemical alterations produced by subchronic exposure to low toluene concentration. To test this hypothesis, we evaluated whether subchronic combined exposure (16 weeks, 104 h per week) to noise at 80 dB-A and toluene at 40 ppm potentiates the recently reported neurotoxic effects of subchronic exposure to 40 ppm toluene. Locomotor and rearing activities, sensitization to narcosis induced by acute toluene at high concentration, and tyrosine and tryptophan hydroxylase activities in the caudate-putamen and hippocampus were investigated in both male and female rats. Our results confirm that subchronic exposure to 40 ppm toluene significantly decreases rearing activity and leads to a sensitization to toluene-induced narcosis, as evaluated by loss of righting reflex, but fails to demonstrate any adverse effect of noise, alone or in combination with toluene. Given that toluene has addictive properties, the lack of potentiating behavioral and neurochemical effect of noise is discussed with regards to a recent study that has shown that methamphetamine neurotoxicity is potentiated by exposure to loud noise.     

Separate detectors for simple and complex grating patterns?

Grating having two sinusoidal components show a periodic variation in contrast which is visible as a "beat" pattern. The spatial frequency of the beat is the difference between the frequencies of the two components. Thresholds for a number of detection and discrimination tasks were measured using beat patterns of 1 c/deg (with components of 9 and 10 c/deg), and gratings of 1 and 10 c/deg. Temporal modulation at 6 Hz lowered detection thresholds for 1 c/deg gratings, but not for beats or 10 c/deg gratings. The effect of contrast on the range of temporal frequencies over which direction of movement can be discriminated differs for the three types of pattern: beats resemble neither low nor high spatial frequency gratings. Low and (for 2 of 3 observers) high spatial frequency gratings, but not beat patterns, are susceptible to a movement after effect induced by a low spatial-frequency grating. Beat patterns induce little or no movement after effect. We conclude that beat patterns are not detected by the same mechanisms that detect simple gratings.     

重庆地区成年女性甲状腺结节检出情况及影响因素分析

目的 了解重庆地区健康体检人群中成年女性的甲状腺结节(thyroid nodules,TNs)检出情况及影响因素,为甲状腺疾病的防治提供参考。方法 分析重庆某大型三甲医院健康体检中心38 069例健康女性体检者甲状腺超声检查情况及代谢相关指标,计算甲状腺结节的检出率并分析其影响因素。结果 38 069例健康女性体检者中,16 042例检出甲状腺结节,检出率为42.1%,多发性甲状腺结节8 908例,占比为55.5%,甲状腺结节的检出率随年龄增长而增加(P<0.01)。多因素logistic 回归分析提示,年龄增加(>30岁)、中心性肥胖(OR=1.16,95%CI:1.08～1.25)、高血压(OR=1.16,95%CI: 1.07～1.25)是甲状腺结节的独立危险因素(P<0.01); 低BMI是甲状腺结节的保护因素(OR=0.89,95%CI: 0.81～0.98, P<0.01)。结论 重庆地区女性甲状腺结节检出率较高,对于高龄、中心型肥胖及高血压女性人群应该重点进行甲状腺结节的超声筛查,以便早期发现和诊断。     

共情护理对女性抑郁症脑电生物反馈治疗患者治疗依从性及生活功能的影响

目的探讨共情护理对女性抑郁症脑电生物反馈治疗患者治疗依从性及生活功能的影响。方法选择2018年1月至2019年6月于我院行脑电生物反馈治疗的女性抑郁症患者98例,根据护理方法不同分为对照组(49例,常规护理)与观察组(49例,共情护理)。比较两组的治疗依从性和生活功能。结果干预后,观察组用药、自我观察、临床护理依从性均高于对照组(P <0.05)。干预后,观察组的躯体功能、心理功能、社会功能、物质生活评分高于对照组(P <0.05)。结论共情护理可提高女性抑郁症脑电生物反馈治疗患者的治疗依从性和生活功能,促进患者恢复。     

FAM19A4基因启动子甲基化检测在宫颈癌及其癌前病变筛查的研究

宫颈癌是最常见的妇科恶性肿瘤之一。目前人乳头瘤病毒(HPV)检测及细胞学检查是宫颈癌及其癌前病变(CCPL)的主要筛查手段。由于上述传统筛查方法,仍然存在对CCPL漏诊的风险,因此寻找有效识别CCPL的特异性分子标志物,具有重要临床意义。对具有序列相似性家族19成员A4(FAM19A4)基因启动子甲基化定量检测,可有效检出CCPL组织,较传统筛查方法有较高特异度,有望成为CCPL筛查的特异性分子标志物。笔者拟就FAM19A4基因启动子甲基化定量检测,在CCPL筛查中应用的最新研究现状进行阐述,旨在为进一步推进CCPL筛查方法的开发,提供思路。     

XPO4、MAP2K4及ZIC1在子宫内膜癌组织表达及其对子宫内膜癌患者预后评估价值

目的探讨输出蛋白(XPO)4、丝裂原活化蛋白激酶(MAP2K)4及小脑锌指结构蛋白(ZIC)1在子宫内膜癌(EC)组织中的表达及其对EC患者的预后评估价值。 方法选择2017年6月至2018年6月,无锡市妇幼保健院、复旦大学附属中山医院青浦分院收治的147例EC患者为研究对象。采用免疫组化染色法检测患者EC组织及癌旁正常组织XPO4、MAP2K4、ZIC1表达水平。采用χ²检验,对患者EC组织及癌旁正常组织XPO4、MAP2K4、ZIC1阳性率,以及不同临床病理特征患者EC组织XPO4、MAP2K4、ZIC1阳性率进行比较。采用Two-stage检验,对EC组织XPO4、MAP2K4、ZIC1呈阳性与呈阴性患者的3年总体生存(OS)率进行比较。本研究遵循的程序经过无锡市妇幼保健院、复旦大学附属中山医院青浦分院伦理委员会批准(审批文号：20160803、20160502)。 结果①本组患者EC组织XPO4、MAP2K4阳性率分别为34.7%(51/147)、38.1%(56/147),显著低于癌旁正常组织的66.7%(98/147)与72.8%(107/147),并且差异均有统计学意义(χ²＝30.060、35.812,P<0.001)。本组患者EC组织ZIC1阳性率为72.1%(106/147),显著高于癌旁正常组织的40.1%(59/147),并且差异亦有统计学意义(χ²＝30.512、P<0.001)。②不同年龄、EC直径及绝经与否患者的EC组织XPO4、MAP2K4、ZIC1阳性率比较,差异均无统计学意义(P>0.05)。不同国际妇产科联盟(FIGO)临床分期、组织病理学分级、子宫肌层侵犯程度及淋巴结转移与否患者EC组织XPO4、MAP2K4、ZIC1阳性率分别比较,差异均有统计学意义(P<0.05)。③本组EC组织XPO4、MAP2K4呈阴性患者的3年OS率分别为42.7%、38.5%,均显著低于XPO4、MAP2K4呈阳性者的68.6%、71.4%,并且差异均有统计学意义(χ²＝8.960、P＝0.003,χ²＝15.077、P<0.001)。EC组织ZIC1呈阳性患者3年OS率为35.8%,显著低于ZIC1呈阴性者的68.3%,并且差异亦有统计学意义(χ²＝12.579、P<0.001)。 结论在EC组织中,XPO4、MAP2K4呈低表达,而ZIC1则呈高表达。XPO4、MAP2K4、ZIC1表达水平与患者组织病理学分级、淋巴结转移、FIGO临床分期、子宫肌层侵犯及3年OS率显著相关,其在评估EC患者发病、进展及预后中具有一定价值。     

阴道微环境失衡与高危型人乳头瘤病毒持续感染

目的探讨阴道微生态失衡与高危型人乳头瘤病毒(HR-HPV)持续感染的关系。 方法选择2014年1月至2015年12月,在四川省科学城医院妇科诊断为HR-HPV感染的240例患者为研究对象,年龄为19~73岁。根据HR-HPV感染状态,将其分为研究组(n＝121,HR-HPV持续感染者)和对照组(n＝119,HR-HPV复查呈阴性者)。采用成组t检验,对2组患者的体重、人体质量指数(BMI)、孕次、产次等进行统计学分析。采用χ²检验,对2组患者的细菌性阴道病(BV)、外阴阴道假丝酵母菌病(VVC)、滴虫性阴道炎(TV)、需氧菌性阴道炎(AV)发生率等进行统计学分析。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。 结果①2组受试者体重、BMI、孕次和产次等一般临床资料比较,差异均无统计学意义(P>0.05)。②研究组患者BV、VVC检出率分别为43.0%(52/121)、38.0%(46/121),明显高于对照组的20.2%(24/119)、15.1%(18/119),2组比较,差异均有统计学意义(χ²＝14.422、16.075,P＝0.002、<0.001)。研究组和对照组患者的TV、AV和混合性感染患者检出率比较,差异均无统计学意义(P>0.05)。 结论BV、VVC与HR-HPV持续性感染密切相关,改善阴道微生态环境可能有助于降低HR-HPV的发生率。