双针刺疗法联合米索前列醇在118例孕足月产妇催产中的应用及对产妇宫颈成熟的影响＊

目的 研究118例孕足月产妇催产中采用双针刺疗法联合米索前列醇的效果对其宫颈成熟的影响。方法 选取2019年6月-2020年6月在我院就诊的足月催产患者118例，按照随机数字分配法分为米索前列醇治疗组和联合治疗组，各59例。米索前列醇治疗组给予米索前列醇片进行治疗，联合治疗组在米索前列醇治疗组的基础上给予双针刺疗法针刺双侧合谷、三阴交穴位。统计两组患者宫颈成熟、子宫活动力、宫口扩张速度、出血量、产程、分娩方式、新生儿情况及催产效率。结果 联合治疗组宫颈口扩张、宫颈管消退、先露位置、宫颈硬度、宫口位置指标均大于米索前列醇治疗组，有统计学差异（P < 0.05）。联合治疗组子宫活动力、宫口扩张速度均大于米索前列醇治疗组，产时出血量、产后2 h出血量均低于米索前列醇治疗组，有统计学差异（P < 0.05）。联合治疗组第一产程、第二产程、第三产程、总产程均小于米索前列醇治疗组，有统计学差异（P < 0.05）。联合治疗组阴道分娩患者例数多于米索前列醇治疗组，剖宫产患者例数少于米索前列醇治疗组，有统计学差异（P < 0.05）。联合治疗组催产效率高于米索前列醇治疗组，有统计学差异（P < 0.05）。结论 双针刺疗法联合米索前列醇在足月产妇催产中应用能促进患者宫颈成熟，减少产后出血量，缩短产程，促进阴道分娩，催产效率高。     

Gestational poly(I:C) attenuates,not exacerbates,the behavioral,cytokine and mTOR changes caused by isolation rearing in a rat ‘dual-hit’ model for neurodevelopmental disorders

Many psychiatric illnesses have a multifactorial etiology involving genetic and environmental risk factors that trigger persistent neurodevelopmental impairments. Several risk factors have been individually replicated in rodents, to understand disease mechanisms and evaluate novel treatments, particularly for poorly-managed negative and cognitive symptoms. However, the complex interplay between various factors remains unclear. Rodent dual-hit neurodevelopmental models offer vital opportunities to examine this and explore new strategies for early therapeutic intervention. This study combined gestational administration of polyinosinic:polycytidylic acid (poly(I:C); PIC, to mimic viral infection during pregnancy) with post-weaning isolation of resulting offspring (to mirror adolescent social adversity). After in vitro and in vivo studies required for laboratory-specific PIC characterization and optimization, we administered 10 mg/kg i.p. PIC potassium salt to time-mated Lister hooded dams on gestational day 15. This induced transient hypothermia, sickness behavior and weight loss in the dams, and led to locomotor hyperactivity, elevated striatal cytokine levels, and increased frontal cortical JNK phosphorylation in the offspring at adulthood. Remarkably, instead of exacerbating the well-characterized isolation syndrome, gestational PIC exposure actually protected against a spectrum of isolation-induced behavioral and brain regional changes. Thus isolation reared rats exhibited locomotor hyperactivity, impaired associative memory and reversal learning, elevated hippocampal and frontal cortical cytokine levels, and increased mammalian target of rapamycin (mTOR) activation in the frontal cortex – which were not evident in isolates previously exposed to gestational PIC. Brains from adolescent littermates suggest little contribution of cytokines, mTOR or JNK to early development of the isolation syndrome, or resilience conferred by PIC. But notably hippocampal oxytocin, which can protect against stress, was higher in adolescent PIC-exposed isolates so might contribute to a more favorable outcome. These findings have implications for identifying individuals at risk for disorders like schizophrenia who may benefit from early therapeutic intervention, and justify preclinical assessment of whether adolescent oxytocin manipulations can modulate disease onset or progression.     

What does basic science tell us about the use of uterotonics?

Pharmacotherapy with uterotonics remains the mainstay of the management for post-partum haemorrhage. Clinical studies evaluating the efficacy of these drugs are fraught with confounders, which may influence uterine contractility and blood loss. For this reason, a range of techniques have been developed to study myometrial function in vitro, allowing for the comparison of various drugs in a controlled-simulated physiological environment.In this review, we focus on the main classes of uterotonic drugs and outline their molecular and physiological basis of action. We explore the evidence related to appropriate drug dosing and relative efficacy, and compare the evidence gleaned from clinical and in vitro studies. We discuss the mechanism of oxytocin desensitisation and how basic science has helped us understand this phenomenon. We also discuss the in vitro research findings for each of the main classes of uterotonic drugs that have contributed to an improved understanding of the management of post-partum haemorrhage and, ultimately, better care for mothers.     

Neuroepigenetic impact on mentalizing in childhood

Mentalizing, or the ability to understand the mental states and intentions of others, is an essential social cognitive function that children learn and continue to cultivate into adolescence. While most typically developing children acquire sufficient mentalizing skills, individual differences in mentalizing persist throughout childhood and are likely influenced by a combination of cognitive functioning, the social environment, and biological factors. DNA methylation of the oxytocin receptor gene (OXTRm) impacts gene expression and is associated with increased brain activity in mentalizing regions during displays of animacy in healthy young adults. The establishment, fine-tuning, and implications of such associations in the context of broader social functioning remain unclear. Using a developmental neuroimaging epigenetic approach, we investigated the contributions of OXTRm to individual variability in brain function during animate motion perception in middle childhood. We find that higher levels of OXTRm are associated with increased neural responses in the left temporo-parietal junction and inferior frontal gyrus. We also find a positive association between neural activity in LTPJ and social skills. These findings provide evidence of epigenetic influence on the developing child brain and demonstrate that variability in neural social perception in childhood is multifaceted with contributions from individual social experience and the endogenous oxytocin system.     

Gene expression of estrogen and oxytocin receptors in the uterus of pregnant and parturient bitches

In the canine species, the precise mechanisms of pregnancy maintenance and the initiation of parturition are not completely understood. The expression of genes encoding the receptors for estrogen (ERα mRNA) and oxytocin (OTR mRNA) was studied in the endometrium and myometrium during pregnancy and parturition in dogs. Real-time PCR was performed to quantify the levels of ERα mRNA and OTR mRNA in the uterus of bitches during early (up to 20 days of gestation), mid (20 to 40 days) and late pregnancy (41 to 60 days), and parturition (first stage of labor). All tissues expressed ERα and OTR mRNA, and are thus possibly able to respond to eventual estrogen and oxytocin hormonal stimuli. No statistically significant differences in the expression of ERα mRNA were verified in the endometrium and myometrium throughout pregnancy and parturition, but expression of OTR mRNA increased at both parturition and late pregnancy. We concluded that the increase of endometrial and myometrial OTR mRNA expression in dogs is not an event dependent on estrogenic stimulation. Moreover, the contractility response of the canine uterus to oxytocin begins during pregnancy and maintains myometrial activity. The expression of OTR mRNA in canine uterine tissues varied over time, which supports an interpretation that the sensitivity and response to hormone therapy varies during the course of pregnancy and labor. Further studies are needed to elucidate the factors underlying the synthesis of uterine oxytocin receptors and the possible role of ERβ rather than ERα in the uterine tissues during pregnancy and parturition in dogs.     

催产素减轻新生大鼠海马神经元缺氧缺血性损伤

目的:探讨催产素(oxytocin)对新生大鼠缺氧缺血性损伤后海马CA1区神经元的作用及机制。方法:采用氧糖剥夺(OGD)制备体外缺氧缺血模型,取8只7~10日龄新生大鼠的急性分离脑片(6~8片/只)随机分为4组,即对照组、OGD 20 min组、OGD 40 min组和OGD+oxytocin组,进行TO-PRO-3染色实验观察催产素对神经元的作用。另取20只新生大鼠脑片随机分为4组,分别是OGD组、OGD+oxytocin组、OGD+d VOT(催产素受体阻断剂)+oxytocin组和OGD+bicuculline(GABAA受体阻断剂)+oxytocin组,用全细胞膜片钳记录不同药物作用下海马神经元缺氧去极化的出现时间。结果:TO-PRO-3染色结果显示海马CA1区神经元死亡数量随着氧糖剥夺时间延长而增加,催产素能显著减少OGD所致的死亡神经元数目(P0.05)。全细胞膜片钳记录结果显示,催产素可使缺氧去极化时间显著延长;d VOT及bicuculline可以消除这种效应。结论:催产素能减轻新生大鼠海马CA1区神经元缺氧缺血性损伤,其机制可能是通过结合催产素受体,增强抑制性神经传递,从而产生神经保护作用。     

Animal models of Central Diabetes Insipidus: Human relevance of acquired beyond hereditary syndromes and the role of oxytocin

The aim of this study was to review different animal models of Central Diabetes Insipidus, a neurobiological syndrome characterized by the excretion of copious amounts of diluted urine (polyuria), a consequent water intake (polydipsia), and a rise in the serum sodium concentration (hypernatremia). In rodents, Central Diabetes Insipidus can be caused by genetic disorders (Brattleboro rats) but also by various traumatic/surgical interventions, including neurohypophysectomy, pituitary stalk compression, hypophysectomy, and median eminence lesions. Regardless of its etiology, Central Diabetes Insipidus affects the neuroendocrine system that secretes arginine vasopressin, a neurohormone responsible for antidiuretic functions that acts trough the renal system. However, most Central Diabetes Insipidus models also show disorders in other neurobiological systems, specifically in the secretion of oxytocin, a neurohormone involved in body sodium excretion.Although the hydromineral behaviors shown by the different Central Diabetes Insipidus models have usually been considered as very similar, the present review highlights relevant differences with respect to these behaviors as a function of the individual neurobiological systems affected. Increased understanding of the relationship between the neuroendocrine systems involved and the associated hydromineral behaviors may allow appropriate action to be taken to correct these behavioral neuroendocrine deficits.     

宫颈扩张球囊联合缩宫素及间苯三酚在足月妊娠引产中的应用效果

目的：分析宫颈扩张球囊联合缩宫素及间苯三酚在足月妊娠引产中的应用效果。方法选取本院妇产科2012年1月~2014年11月接收的136例符合引产指征的的足月妊娠初产妇,根据其意愿将其分为对照组(n=74)和观察组(n=62)。对照组患者于宫颈评分后给予0.5%缩宫素,潜伏期给予间苯三酚;观察组在对照组基础上放置Cook双球囊。比较两组产妇干预前后的宫颈 Bishop评分;干预12 h后,比较两组产妇的促宫颈成熟效果;比较两组产妇的引产效果、分娩方式及妊娠结局;比较两组产妇的产程情况。结果干预前,两组的宫颈 Bishop评分比较差异无统计学意义(P>0.05),干预后,观察组显著高于对照组(P<0.05)。观察组的促宫颈成熟效果显著优于对照组(P<0.05)。观察组12 h内临产、阴道分娩的比例显著高于对照组(P<0.05),产后尿潴留、产后出血、胎儿窘迫、新生儿窒息等妊娠结局发生率显著低于对照组(P<0.05)。除第二产程外,观察组产妇的产程均显著短于对照组(P<0.05)。结论宫颈扩张球囊联合缩宫素及间苯三酚能够提高宫颈 Bishop评分,提高阴道分娩成功率,降低不良妊娠结局发生率。     

Methylation of the oxytocin receptor gene in clinically depressed patients compared to controls: The role of OXTR rs53576 genotype

The emerging field of epigenetics provides a biological basis for gene-environment interactions relevant to depression. We focus on DNA methylation of exon 1 and 2 of the oxytocin receptor gene (OXTR) promoter. The research aims of the current study were to compare OXTR DNA methylation of depressed patients with healthy control subjects and to investigate possible influences of the OXTR rs53576 genotype. The sample of the present study consisted of 43 clinically depressed women recruited from a psychosomatic inpatient unit and 42 healthy, female control subjects – mean age 30 years (SD = 9). DNA methylation profiles of the OXTR gene were assessed from leukocyte DNA by means of bisulfite sequencing. Depressed female patients had decreased OXTR exon 1 DNA methylation compared to non-depressed women. The association between depression and methylation level was moderated by OXTR rs53576 genotype. Exon 2 methylation was associated with OXTR rs53576 genotype but not with depression. Our findings suggest exon-specific methylation mechanisms. Exon 1 methylation appears to be associated with depressive phenotypes whereas exon 2 methylation is influenced by genotype. Previously reported divergent associations between OXTR genotype and depression might be explained by varying exon 1 methylation. In order to further understand the etiology of depression, research on the interplay between genotype, environmental influences and exon-specific methylation patterns is needed.     

Neuropeptides in the posterodorsal medial amygdala modulate central cardiovascular reflex responses in awake male rats

The rat posterodorsal medial amygdala (MePD) links emotionally charged sensory stimuli to social behavior, and is part of the supramedullary control of the cardiovascular system. We studied the effects of microinjections of neuroactive peptides markedly found in the MePD, namely oxytocin (OT, 10 ng and 25 pg; n=6/group), somatostatin (SST, 1 and 0.05 μM; n=8 and 5, respectively), and angiotensin II (Ang II, 50 pmol and 50 fmol; n=7/group), on basal cardiovascular activity and on baroreflex- and chemoreflex-mediated responses in awake adult male rats. Power spectral and symbolic analyses were applied to pulse interval and systolic arterial pressure series to identify centrally mediated sympathetic/parasympathetic components in the heart rate variability (HRV) and arterial pressure variability (APV). No microinjected substance affected basal parameters. On the other hand, compared with the control data (saline, 0.3 µL; n=7), OT (10 ng) decreased mean AP (MAP₅₀) after baroreflex stimulation and increased both the mean AP response after chemoreflex activation and the high-frequency component of the HRV. OT (25 pg) increased overall HRV but did not affect any parameter of the symbolic analysis. SST (1 μM) decreased MAP₅₀, and SST (0.05 μM) enhanced the sympathovagal cardiac index. Both doses of SST increased HRV and its low-frequency component. Ang II (50 pmol) increased HRV and reduced the two unlike variations pattern of the symbolic analysis (P<0.05 in all cases). These results demonstrate neuropeptidergic actions in the MePD for both the increase in the range of the cardiovascular reflex responses and the involvement of the central sympathetic and parasympathetic systems on HRV and APV.