Metabolism alteration in follicular niche: The nexus among intermediary metabolism,mitochondrial function,and classic polycystic ovary syndrome

Classic polycystic ovary syndrome (PCOS) is a high-risk phenotype accompanied by increased risks of reproductive and metabolic abnormalities; however, the local metabolism characteristics of the ovaries and their effects on germ cell development are unclear. The present study used targeted metabolomics to detect alterations in the intermediate metabolites of follicular fluid from classic PCOS patients, and the results indicated that hyperandrogenism but not obesity induced the changed intermediate metabolites in classic PCOS patients. Regarding the direct contact, we identified mitochondrial function, redox potential, and oxidative stress in cumulus cells which were necessary to support oocyte growth before fertilization, and suggested dysfunction of mitochondria, imbalanced redox potential, and increased oxidative stress in cumulus cells of classic PCOS patients. Follicular fluid intermediary metabolic profiles provide signatures of classic PCOS ovary local metabolism and establish a close link with mitochondria dysfunction of cumulus cells, highlighting the role of metabolic signal and mitochondrial cross talk involved in the pathogenesis of classic PCOS.     

Mitochondrial toxicity and caspase activation in HIV pregnant women

To assess the impact of HIV‐infection and highly active anti‐retroviral treatment in mitochondria and apoptotic activation of caspases during pregnancy and their association with adverse perinatal outcome. Changes of mitochondrial parameters and apoptotic caspase activation in maternal peripheral blood mononuclear cells were compared at first trimester of pregnancy and delivery in 27 HIV‐infected and ‐treated pregnant women versus 24 uninfected pregnant controls. We correlated immunovirological, therapeutic and perinatal outcome with experimental findings: mitochondrial DNA (mtDNA) content, mitochondrial protein synthesis, mitochondrial function and apoptotic caspase activation. The HIV pregnancies showed increased adverse perinatal outcome (OR: 4.81 [1.14–20.16]; P < 0.05) and decreased mtDNA content (42.66 ± 5.94%, P < 0.01) compared to controls, even higher in naïve participants. This depletion caused a correlated decrease in mitochondrial protein synthesis (12.82 ± 5.73%, P < 0.01) and function (20.50 ± 10.14%, P < 0.001), not observed in controls. Along pregnancy, apoptotic caspase‐3 activation increased 63.64 ± 45.45% in controls (P < 0.001) and 100.00 ± 47.37% in HIV‐pregnancies (P < 0.001), in correlation with longer exposure to nucleoside analogues. HIV‐infected women showed increased obstetric problems and declined genetic and functional mitochondrial parameters during pregnancy, especially those firstly exposed to anti‐retrovirals. The apoptotic activation of caspases along pregnancy is emphasized in HIV pregnancies promoted by nucleoside analogues. However, we could not demonstrate direct mitochondrial or apoptotic implication in adverse obstetric outcome probably because of the reduced sample size.     

Ethical Considerations for Outcome‐adaptive Trial Designs: A Clinical Researcher's Perspective

In a typical comparative clinical trial the randomization scheme is fixed at the beginning of the study, and maintained throughout the course of the trial. A number of researchers have championed a randomized trial design referred to as ‘outcome‐adaptive randomization.’ In this type of trial, the likelihood of a patient being enrolled to a particular arm of the study increases or decreases as preliminary information becomes available suggesting that treatment may be superior or inferior. While the design merits of outcome‐adaptive trials have been debated, little attention has been paid to significant ethical concerns that arise in the conduct of such studies. These include loss of equipoise, lack of processes for adequate informed consent, and inequalities inherent in the research design which could lead to perceptions of injustice that may have negative implications for patients and the research enterprise. This article examines the ethical difficulties inherent in outcome‐adaptive trials.     

Model misspecification and bias for inverse probability weighting estimators of average causal effects

Commonly used semiparametric estimators of causal effects specify parametric models for the propensity score (PS) and the conditional outcome. An example is an augmented inverse probability weighting (IPW) estimator, frequently referred to as a doubly robust estimator, because it is consistent if at least one of the two models is correctly specified. However, in many observational studies, the role of the parametric models is often not to provide a representation of the data-generating process but rather to facilitate the adjustment for confounding, making the assumption of at least one true model unlikely to hold. In this paper, we propose a crude analytical approach to study the large-sample bias of estimators when the models are assumed to be approximations of the data-generating process, namely, when all models are misspecified. We apply our approach to three prototypical estimators of the average causal effect, two IPW estimators, using a misspecified PS model, and an augmented IPW (AIPW) estimator, using misspecified models for the outcome regression (OR) and the PS. For the two IPW estimators, we show that normalization, in addition to having a smaller variance, also offers some protection against bias due to model misspecification. To analyze the question of when the use of two misspecified models is better than one we derive necessary and sufficient conditions for when the AIPW estimator has a smaller bias than a simple IPW estimator and when it has a smaller bias than an IPW estimator with normalized weights. If the misspecification of the outcome model is moderate, the comparisons of the biases of the IPW and AIPW estimators show that the AIPW estimator has a smaller bias than the IPW estimators. However, all biases include a scaling with the PS-model error and we suggest caution in modeling the PS whenever such a model is involved. For numerical and finite sample illustrations, we include three simulation studies and corresponding approximations of the large-sample biases. In a dataset from the National Health and Nutrition Examination Survey, we estimate the effect of smoking on blood lead levels.     

重症肺炎患者病原菌分布、临床结局分析及血清尿素氮与肌酐比值、尿素氮与白蛋白比值联合检测的临床意义

摘要 目的：分析重症肺炎（SP）患者病原菌分布和临床结局并探讨血清尿素氮与肌酐比值（UCR）、尿素氮与白蛋白比值（UAR）联合检测的临床意义。方法：选取2019年8月～2022年8月三六三医院收治的107例SP患者,根据临床结局分为死亡组和存活组。分析SP患者病原菌分布情况。采用单因素和多因素Logistic回归分析SP患者临床结局的影响因素,采用受试者工作特征（ROC）曲线分析血清UCR、UAR水平对SP患者临床结局的评估价值。结果：107例SP患者痰液标本中培养出122株病原菌,其中革兰阴性菌75株（61.48%）,革兰阳性菌39株（31.97%）,真菌8株（6.56%）。107例SP患者院内死亡率为40.19%（43/107）。多因素Logistic回归分析显示,年龄增加、肺外并发症≥2个和UCR、UAR升高为SP患者临床结局不良的独立危险因素,氧合指数增加为其独立保护因素（P＜0.05）。ROC曲线分析显示,血清UCR、UAR联合评估SP患者临床结局的曲线下面积（AUC）大于各指标单独评估。结论：SP患者病原菌分布以革兰阴性菌为主,血清UCR、UAR升高为SP患者临床结局不良的独立危险因素,可能成为SP患者临床结局的辅助评估指标,且二者联合评估SP患者临床结局的价值较高。     

游离睾酮指数联合血清GnSAF、SHBG对多囊卵巢综合征不孕患者IVF-ET治疗妊娠结局的预测价值

摘要 目的：探讨游离睾酮指数（FAI）联合血清促性腺激素平抑因子（GnSAF）、性激素结合球蛋白（SHBG）对多囊卵巢综合征（PCOS）不孕患者体外受精-胚胎移植（IVF-ET）治疗妊娠结局的预测价值。方法：选取2020年1月～2022年6月湖南省妇幼保健院生殖医学中心收治的197例PCOS不孕患者为PCOS组,根据IVF-ET治疗妊娠结局分为妊娠失败组和妊娠成功组,另选取同期68名体检健康妇女为对照组。收集PCOS不孕患者临床资料,计算FAI并检测血清GnSAF、SHBG水平。采用单因素和多因素Logistic回归分析PCOS不孕患者IVF-ET治疗妊娠结局的影响因素,采用受试者工作特征（ROC）曲线分析FAI和血清GnSAF、SHBG对PCOS不孕患者IVF-ET治疗妊娠结局的预测价值。结果：PCOS组FAI和血清GnSAF水平高于对照组,SHBG水平低于对照组（P＜0.05）。197例PCOS不孕患者IVF-ET治疗妊娠成功率为51.27%（101/197）。单因素分析显示,妊娠失败组体质指数、黄体生成素（LH）、LH/促卵泡生成素（FSH）、睾酮、抗苗勒管激素（AMH）、FAI、GnSAF高于妊娠成功组,FSH、受精率、优胚率、SHBG低于妊娠成功组（P＜0.05）。多因素Logistic回归分析显示,体质指数增加和LH、LH/FSH、AMH、FAI、GnSAF升高为PCOS不孕患者IVF-ET治疗妊娠失败的独立危险因素,SHBG升高为其独立保护因素（P＜0.05）。ROC曲线分析显示,FAI和血清GnSAF、SHBG联合预测PCOS不孕患者IVF-ET治疗妊娠结局的曲线下面积大于FAI、GnSAF、SHBG单独预测。结论：FAI和血清GnSAF、SHBG水平联合预测PCOS不孕患者IVF-ET治疗妊娠结局的价值较高。     

Construct Validity of the Impact of Weight on Quality of Life Questionnaire

KOLOTKIN, RONETTE L, SUSAN HEAD, ALAN BROOKHART. Construct validity of the Impact of Weight on Quality of Life questionnaire. The Impact of Weight on Quality of Life questionnaire (IWQOL) is a 74-item self-report, condition-specific instrument that (1) assesses the effect of weight on quality of life in eight key areas, and (2) may be used as a treatment outcome measure and/or an evaluation tool for healthcare policy makers and third-party payers. This study explores IWQOL construct validity and provides new information on internal consistency, treatment effects, and differences between men and women. IWQOL total scores correlated highly with other measures of overall quality of life, and subscale scores correlated well with counterparts in the assessment battery. Internal consistency estimates for the IWQOL scales generally were high. For the women, 4-week participants, and the total sample, pretreatment-posttreatment differences were significant for all IWQOL scales and total score. For men, treatment differences were significant for the total score and all subscales except for Work and Mobility. Treatment differences for 2-week participants were significant for all scales except for Work. Consistent with previous IWQOL study results, the Comfort With Food scale scores reflected more discomfort at posttreatment as compared with pretreatment. The IWQOL, already translated into French and Italian, currently is demonstrating clinical and research utility as a quality-of-life outcome measure for clinical trials of antiobesity drugs and surgical treatments for patients with obesity.     

Epigenetic regulation of the placental HSD11B2 barrier and its role as a critical regulator of fetal development

“Fetal programming” is a term used to describe how early-life experience influences fetal development and later disease risk. In humans, prenatal stress-induced fetal programming is associated with increased risk of preterm birth, and a heightened risk of metabolic and neurological diseases later in life. A critical determinant of this is the regulation of fetal exposure to glucocorticoids by the placenta. Glucocorticoids are the mediators through which maternal stress influences fetal development. Excessive fetal glucocorticoid exposure during pregnancy results in low birth weight and abnormalities in a number of tissues. The amount of fetal exposure to maternal glucocorticoids depends on the expression of HSD11B2, an enzyme predominantly produced by the syncytiotrophoblast in the placenta. This protects the fetus by converting active glucocorticoids into inactive forms. In this review we examine recent findings regarding placental HSD11B2 that suggest that its epigenetic regulation may mechanistically link maternal stress and long-term health consequences in affected offspring.     

持续镇痛分娩对产妇分娩结局和新生儿评分的影响

目的:研究持续镇痛分娩对产妇分娩结局和新生儿评分的影响。方法:选择2018年7月～2019年7月中国医科大学航空总医院(本院)采取硬膜外分娩镇痛的101例产妇,将其随机分为两组。当产生确切的镇痛效果,进入第二产程后,观察组的51例产妇采用0.4μg/m L舒芬太尼以及0.08%罗哌卡因进行持续镇痛分娩;对照组的50例产妇则在宫口开全后,使用生理盐水替代泵内的局麻药物,直到分娩结束。比较两组产妇催产素的使用率,宫口扩张度和第一、第二产程按压硬膜外自控镇痛泵的次数,分娩方式,新生儿的体质量,脐动脉血pH值,出生后1 min和5 min Apgar评分,产妇修复会阴部时的视觉模拟评分(visual analogue scale, VAS)评分及产妇对于第二产程镇痛的满意度评分。结果:两组产妇催产素的使用率、宫口扩张度和第一、第二产程按压硬膜外自控镇痛泵的次数、分娩方式(剖宫产率、器械助产率、自然分娩率)、第一产程镇痛时间、第一以及第二产程时间相比均无显著差异(P0.05);两组新生儿的体质量,脐动脉血pH值,出生后1 min和5 min Apgar评分小于8分的新生儿所占的比例相比没有明显的差异(P0.05);观察组产妇修复会阴部时的VAS评分明显低于对照组(P0.05),产妇对于第二产程镇痛的满意度评分明显高于对照组(P0.05)。结论:持续镇痛分娩对产妇分娩结局和新生儿评分无明显的影响,但可显著提高产妇对第二产程镇痛和修复会阴部时镇痛的满意度。     

Clinical features and hematological findings of COVID-19 patients with blood transfusion

This paper aims to illustrate the clinical characteristics, hematological findings, and blood transfusion information of Coronavirus disease 2019 (COVID-19) patients. Twenty-three COVID-19 patients were treated and transfused with blood products in Wuhan First Hospital from February 12 to March 20, 2020. The patients were divided into a survivor group and a non-survivor group, respectively, according to whether the patient had been discharged or died. The results demonstrated at the time of initial blood transfusion, that the non-survivor group possessed a lower platelet (PLT) than that of the survivor group (P<0.001), and PLT were below the normal range in 6 (85.7%) non-survivor group and in 2 (12.5%) survivor group (P<0.01). Over half of these patients had abnormalities in fibrinogen (FIB), activated partial thromboplastin time (APTT), prothrombin time (PT), and international normalized ratio (INR), but no significant difference was found between the non-survivor group and survivor group. The non-survivor group had a dramatically higher D-Dimers and disseminated intravascular coagulation (DIC) scores than those of the survivor group (P<0.01). Six (85.7%) non-survivors but none of the survivors had a DIC score greater than 6 (P<0.001). Fifteen (93.8%) survivors and 2 (28.6%) non-survivors were transfused with RBC (P<0.01). The non-survivors (5/7) possessed a higher proportion for using AP than the survivors (2/16). The study suggests that COVID-19 patients who undergo blood transfusion usually possess coagulation dysfunction, and DIC may be closely related to deteriorating clinical outcomes.