Fetal and neonatal programming of postnatal growth and feed efficiency in swine

Maternal undernutrition or overnutrition during pregnancy alters organ structure, impairs prenatal and neonatal growth and development, and reduces feed efficiency for lean tissue gains in pigs. These adverse effects may be carried over to the next generation or beyond. This phenomenon of the transgenerational impacts is known as fetal programming, which is mediated by stable and heritable alterations of gene expression through covalent modifications of DNA and histones without changes in DNA sequences(namely, epigenetics). The mechanisms responsible for the epigenetic regulation of protein expression and functions include chromatin remodeling; DNA methylation(occurring at the 5′-position of cytosine residues within CpG dinucleotides); and histone modifications(acetylation, methylation, phosphorylation, and ubiquitination). Like maternal malnutrition, undernutrition during the neonatal period also reduces growth performance and feed efficiency(weight gain:feed intake; also known as weightgain efficiency) in postweaning pigs by 5–10%, thereby increasing the days necessary to reach the market bodyweight. Supplementing functional amino acids(e.g., arginine and glutamine) and vitamins(e.g., folate) play a key role in activating the mammalian target of rapamycin signaling and regulating the provision of methyl donors for DNA and protein methylation. Therefore, these nutrients are beneficial for the dietary treatment of metabolic disorders in offspring with intrauterine growth restriction or neonatal malnutrition. The mechanism-based strategies hold great promise for the improvement of the efficiency of pork production and the sustainability of the global swine industry.

Fetal programming of polycystic ovary syndrome

Polycystic ovary syndrome(PCOS) is a common endocrine disorder that affects up to 6.8% of reproductive age women.Experimental research and clinical observations suggest that PCOS may originate in the very early stages of development,possibly even during intrauterine life.This suggests that PCOS is either genetically-transmittedor is due to epigenetic alterations that develop in the intrauterine microenvironment.Although familial cases support the role of genetic factors,no specific genetic pattern has been defined in PCOS.Several candidate genes have been implicated in its pathogenesis,but none can specifically be implicated in PCOS development.Hypotheses based on the impact of the intrauterine environment on PCOS development can be grouped into two categories.The first is the "thrifty" phenotype hypothesis,which states that intrauterine nutritional restriction in fetuses causes decreased insulin secretion and,as a compensatory mechanism,insulin resistance.Additionally,an impaired nutritional environment can affect the methylation of some specific genes,which can also trigger PCOS.The second hypothesis postulates that fetal exposure to excess androgen can induce changes in differentiating tissues,causing the PCOS phenotype to develop in adult life.This review aimed to examine the role of fetal programming in development of PCOS.

Fetal programming and early identification of newborns at high risk of free radical-mediated diseases

Nowadays metabolic syndrome represents a real outbreak affecting society. Paradoxically, pediatricians must feel involved in fighting this condition because of the latest evidences of developmental origins of adult diseases. Fetal programming occurs when the normal fetal development is disrupted by an abnormal insult applied to a critical point in intrauterine life. Placenta assumes a pivotal role in programming the fetal experience in utero due to the adaptive changes in structure and function. Pregnancy complications such as diabetes, intrauterine growth restriction, preeclampsia, and hypoxia are associated with placental dysfunction and programming. Many experimental studies have been conducted to explain the phenotypic consequences of fetal-placental perturbations that predispose to the genesis of metabolic syndrome, obesity, diabetes, hyperinsulinemia, hypertension, and cardiovascular disease in adulthood. In recent years, elucidating the mechanisms involved in such kind of process has become the challenge of scientific research. Oxidative stress may be the general underlying mechanism that links altered placental function to fetal programming. Maternal diabetes, prenatal hypoxic/ischaemic events, inflammatory/infective insults are specific triggers for an acute increase in free radicals generation. Early identification of fetuses and newborns at high risk of oxidative damage may be crucial to decrease infant and adult morbidity.

Endocrine Disruptors and Fetal Programming

The concept “fetal programming” shows who still in the intrauterine life, can interfere in factors related to the genesis and development of diseases in childhood, adolescence and adult life. The literature shows that children born to mothers with gestational diabetes mellitus (GDM) are at increased risk for the development of obesity in adulthood, it becomes fundamental to study more about the subject. Obesity is a disease of multifactorial etiology, resulting from complex interactions between genetic and environmental factors. However, the marked increase in its incidence, precocity and severity are not yet fully understood. Several findings suggest that stressor stimuli (e.g. diabetes, nutritional changes) during intrauterine development may promote epigenetic changes, as well as affect mitochondrial metabolism, which may modulate fetal development and predispose to the late development of diseases. Despite the considerable amount of evidence accumulated about intrauterine programming for diseases of adult life, the determinant mechanisms of such programming are not yet clear.

Maternal low protein diet and fetal programming of lean type 2 diabetes

Maternal nutrition is found to be the key factor that determines fetal health in utero and metabolic health during adulthood.Metabolic diseases have been primarily attributed to impaired maternal nutrition during pregnancy,and impaired nutrition has been an immense issue across the globe.In recent years,type 2 diabetes(T2D)has reached epidemic proportion and is a severe public health problem in many countries.Although plenty of research has already been conducted to tackle T2D which is associated with obesity,little is known regarding the etiology and pathophysiology of lean T2D,a variant of T2D.Recent studies have focused on the effects of epigenetic variation on the contribution of in utero origins of lean T2D,although other mechanisms might also contribute to the pathology.Observational studies in humans and experiments in animals strongly suggest an association between maternal low protein diet and lean T2D phenotype.In addition,clear sex-specific disease prevalence was observed in different studies.Consequently,more research is essential for the understanding of the etiology and pathophysiology of lean T2D,which might help to develop better disease prevention and treatment strategies.This review examines the role of protein insufficiency in the maternal diet as the central driver of the developmental programming of lean T2D.

Stage-specific nutritional management and developmental programming to optimize meat production

Over the past few decades,genetic selection and refined nutritional management have extensively been used to increase the growth rate and lean meat production of livestock.However,the rapid growth rates of modern breeds are often accompanied by a reduction in intramuscular fat deposition and increased occurrences of muscle abnor‑malities,impairing meat quality and processing functionality.Early stages of animal development set the long‑term growth trajectory of offspring.However,due to the seasonal reproductive cycles of ruminant livestock,gestational nutrient deficiencies caused by seasonal variations,frequent droughts,and unfavorable geological locations nega‑tively affect fetal development and their subsequent production efficiency and meat quality.Therefore,enrolling live‑stock in nutritional intervention strategies during gestation is effective for improving the body composition and meat quality of the offspring at harvest.These crucial early developmental stages include embryonic,fetal,and postnatal stages,which have stage‑specific effects on subsequent offspring development,body composition,and meat quality.This review summarizes contemporary research in the embryonic,fetal,and neonatal development,and the impacts of maternal nutrition on the early development and programming effects on the long‑term growth performance of livestock.Understanding the developmental and metabolic characteristics of skeletal muscle,adipose,and fibrotic tissues will facilitate the development of stage‑specific nutritional management strategies to optimize production efficiency and meat quality.

健康和疾病的发育起源理论研究进展

基于生活环境、健康和疾病在分子水平上密切相关的核心理念,健康和疾病的发育起源(developmental origins of health and disease,DOHaD)理论为健康与疾病间的关联研究提供了全新视角。该理论通过多学科、多领域的知识互通,追溯不同的生活经历如何影响生命全过程中的健康和疾病风险。成人期疾病的敏感窗口期不再局限于妊娠前和妊娠期,分娩期至成年早期也成为暴露因素发挥作用的重要时段。母源性/父源性因素、环境因素、新生儿出生状况、儿童期代谢情况等能够通过影响表观遗传、代谢和免疫调控、氧化应激等,改变发育程序并对子代远期健康产生正向或负向影响。因此,为实现健康促进,需要同步推进早期生命阶段预防、后期随访及健康干预的关口前移,以期有效降低成年期疾病风险,提升生命全周期健康水平。综述DOHaD领域最新研究进展对阐明人类发展早期阶段发生的不良事件影响健康和疾病模式及发现有效干预措施具有积极意义。

Mechanisms of developmental programming of the metabolic syndrome and related disorders

There is consistent epidemiological evidence linking low birth weight, preterm birth and adverse fetal growth to an elevated risk of the metabolic syndrome (obesity, raised blood pressure, raised serum triglycerides, lowered serum high-density lipoprotein cholesterol and impaired glucose tolerance or insulin resistance) and related disorders. This "fetal or developmental origins/programming of disease" concept is now well accepted but the "programming" mechanisms remain poorly understood. We reviewed the major evidence, implications and limitations of current hypotheses in interpreting developmental programming and discuss future research directions. Major current hypotheses to interpret developmental programming include: (1)thrifty phenotype; (2) postnatal accelerated or catchup growth; (3) glucocorticoid effects; (4) epigenetic changes; (5) oxidative stress; (6) prenatal hypoxia; (7) placental dysfunction; and (8) reduced stem cell number. Some hypothetical mechanisms (2, 4 and 8) could be driven by other upstream "driver" mechanisms. There is a lack of animal studies addressing multiple mechanisms simultaneously and a lack of strong evidence linking clinical outcomes to biomarkers of the proposed programming mechanisms in humans. There are needs for (1) experimental studies addressing multiple hypothetical mechanisms simultaneously; and (2) prospective pregnancy cohort studies linking biomarkers of the proposed mechanisms to clinical outcomes or surrogate biomarker endpoints. A better understanding of the programming mechanisms is a prerequisite for developing early life interventions to arrest the increasing epidemic of the metabolic syndrome, type 2 diabetes and other related disorders.

Is perinatal neuroendocrine programming involved in the developmental origins of metabolic disorders?

The discovery that small size at birth and during infancy are associated with a higher risk of diabetes and related metabolic disease in later life has pointed to the importance of developmental factors in these conditions. The birth size associations are thought to refl ect exposure to adverse environmental factors during early development but the mechanisms involved are still not fully understood. Animal and human work has pointed to the importance of changes in the setpoint of a number of key hormonal systems controlling growth and development. These include the IGF-1/GH axis, gonadal hormones and, in particular, the systems mediating the classical stress response. Several studies show that small size at birth is linked with increased activity of the hypothalamic-pituitary-adrenal axis and sympathoadrenal system in adult life. More recent human studies have shown associations between specif ic adverse experiences during pregnancy, such as famine or the consumption of adverse diets, and enhanced stress responses many decades later. The mediators of these neuroendocrine responses are biologically potent and are likely to have a direct infl uence on the risk of metabolic disease. These neuroendocrine changes may also have an evolutionary basis being part of broader process, termed phenotypic plasticity, by which adverse environmental cues experienced during development modify the structure and physiology of the adult towards a phenotype adapted for adversity. The changes are clearly advantageous if they lead to a phenotype which is well-adapted for the adult environment, but may lead to disease if there is subsequent overnutrition or other unexpected environmental conditions.

Programming Logic Modeling and Cross-Program Defect Detection Method for Object-Oriented Code

Code defects can lead to software vulnerability and even produce vulnerability risks.Existing research shows that the code detection technology with text analysis can judge whether object-oriented code files are defective to some extent.However,these detection techniques are mainly based on text features and have weak detection capabilities across programs.Compared with the uncertainty of the code and text caused by the developer’s personalization,the programming language has a stricter logical specification,which reflects the rules and requirements of the language itself and the developer’s potential way of thinking.This article replaces text analysis with programming logic modeling,breaks through the limitation of code text analysis solely relying on the probability of sentence/word occurrence in the code,and proposes an object-oriented language programming logic construction method based on method constraint relationships,selecting features through hypothesis testing ideas,and construct support vector machine classifier to detect class files with defects and reduce the impact of personalized programming on detection methods.In the experiment,some representative Android applications were selected to test and compare the proposed methods.In terms of the accuracy of code defect detection,through cross validation,the proposed method and the existing leading methods all reach an average of more than 90%.In the aspect of cross program detection,the method proposed in this paper is superior to the other two leading methods in accuracy,recall and F1 value.

Impact of Educational Programs about Methods of Assessment of Fetal Wellbeing during Pregnancy among Staff Nurses

Objective: Aims of the study are to study the impact of increased knowledge and awareness among staff nurses towards assessment of methods of fetal wellbeing to early identification of pregnancy outcomes and the frequency of interventions during delivery. Design: A quasi-experimental design was used in carrying out the study to impact knowledge and awareness assessment of methods of fetal wellbeing among staff nurses. The study was conducted at obstetric & gynecological department working at setting in Jarsh Governorate Hospitals & Prince Hussein Bin Abdullah Hospitals. Methods: The study sample consisted of all staff nurses working at obstetric & gynecological department in Jarsh Governorate Hospital & Prince Hussein Bin Abdullah Hospitals who have agreed to participate in the study. The current study has included 150 staff types of sample convenient sample. Results: The main findings of this study showed that there is a highly statistical significance differences between pre-test and post-test in all answers regarding knowledge about methods of fetal wellbeing assessment. Conclusion: Nurses have a major role to prevent the complication for the fetus and mother during pregnancy. Nurses coming in contact with the antenatal mothers should take initiative to provide necessary information to the women and the relatives on different methods used for the assessment of fetal wellbeing, so as to improve the quality of life among the pregnant women. For that they should adequate knowledge about all the aspects of fetal wellbeing, so that they can prevent the complication.

经肝动脉化疗栓塞联合程序性死亡受体1抑制剂治疗晚期肝癌的临床研究

目的 探讨经肝动脉化疗栓塞(transhepatic arterial chemoembolization,TACE)联合程序性死亡受体1(programmed deathreceptor1,PD-1)抑制剂治疗晚期肝癌的临床疗效。方法 选择2020年4月至2022年1月甘肃省肿瘤医院收治的80例晚期肝癌患者,采用随机数字表法分为两组,每组40例。对照组采用TACE治疗,观察组采用TACE联合PD-1抑制剂治疗。比较两组的实体瘤疗效、安全性、生存时间,以及治疗前和治疗2个周期后血清血管内皮生长因子(vascular endothelial growth factor,VEGF)、甲胎蛋白(alpha fetal protein,AFP)水平。结果 观察组疾病控制率(75.00%)高于对照组(52.50%),差异有显著性(P<0.05)。两组治疗2个周期后血清VEGF、AFP水平均较治疗前降低,且观察组低于对照组,差异有显著性(P<0.05)。两组Ⅲ度及以上不良反应发生率比较差异无显著性(P>0.05)。80例患者的随访时间为13(1,22)个月,观察组无进展生存时间为7(5,13)个月,长于对照组的5(3,10)个月,差异有显著性(P<0.05)。观察组总生存时间为15(15,22)个月,与对照组的14(13,21)个月比较差异无显著性(P>0.05)。结论 TACE联合PD-1抑制剂治疗晚期肝癌可降低血清VEGF和AFP水平,提高疾病控制率,延长无进展生存时间,且安全性可控。

产前母亲心理压力对儿童心理行为发展影响的研究述评

产前母亲心理压力对儿童心理行为发展有着重要的影响。大量的研究证据表明,产前母亲的心理应激,对后代的情感或认知发展会产生消极的影响,如容易出现注意力缺陷/活动过度、焦虑、语言迟缓等问题。这种影响的潜在机制之一是下丘脑-垂体-肾上腺(HPA)轴的变化,另一个机制可能是,母亲压力或焦虑引起交感-肾上腺系统高度激活。关于产前母亲心理压力对儿童心理行为发展影响的研究,在方法学上存在一定的缺陷,也还有一些未明确的问题,如产前压力的敏感期、性别特异性效应等。未来这一领域应该开发更多的研究途径。已有的证据足以表明,应该积极开展关于预防、干预和支持性方案方面的研究,以减轻妊娠期的压力或焦虑及其对儿童发展的不利影响。

胎儿生长受限与成年后卵巢储备功能的关系

目的探讨胎儿生长受限与成年后卵巢储备功能下降的关系,筛选卵巢储备功能下降的高危人群,对其提供早期临床干预具有重要意义。方法于我院健康体检人群中随机选取18~40岁FGR患者44例（其中18~29周岁妇女30例,30~40周岁妇女14例）,以1∶2成组配对原则在相应年龄段内随机选取非FGR妇女88例（其中18~29周岁妇女60例,30~40周岁妇女28例）,于月经周期的第3~5天之间进行血液样品的采集,采用酶联免疫吸附法（ELISA）检测其血清抑制素-B（INH-B）、抗苗勒管激素（AMH）、促卵泡激素（FSH）水平,并采用（经阴道或腹部）超声检查方式对所有研究对象卵巢的窦卵泡数（AFC）进行测量,对卵巢储备功能进行监测。结果 INH-B、AMH、FSH激素水平、AFC在FGR组与对照组间存在差异,FGR组的FSH值明显大于对照组（P〈0.05）。FGR组的INH-B、AMH值、AFC明显小于对照组（P〈0.05）,差异具有统计学意义。结论胎儿生长受限将会影响成年后的生殖内分泌功能,对成年后卵巢储备功能具有一定的影响。

宫内慢性缺氧对子代大鼠血压的影响

目的探讨宫内慢性缺氧对子代大鼠血压的影响。方法 SD大鼠孕鼠于妊娠第7~21天,每日置于氧气浓度为10%±1%的低压氧舱3 h,待分娩后观测其子代大鼠体重、主要脏器重量及血压的变化。结果宫内缺氧组仔鼠出生后第1天体重显著低于对照组（P〈0.01）,但出生后第20天体重与对照组无显著性差异;宫内缺氧组仔鼠肝脏于出生后第1、20天以及雄性仔鼠肾脏于出生后3月、7月的重量显著低于对照组（P〈0.05）;5月龄、7月龄宫内缺氧组子代雄性大鼠血压均比同性别对照组显著升高（P〈0.05）,且呈现随年龄增长而逐渐加重趋势,但宫内缺氧子代雌性大鼠血压与对照组相比无显著性差异。结论慢性宫内缺氧可能是引起大鼠肝、肾、血管组织程序控制的应激因素之一。它可诱发子代雄性大鼠血压升高,呈现性别依赖现象,并随年龄增长有逐渐加重倾向。

足月胎膜早破孕妇的分娩方案与母婴结局研究

目的探究足月胎膜早破孕妇的分娩方案与母婴结局。方法选取2014年6月至2016年6月于南京市浦口区中心医院妇产科住院分娩的孕妇1 254例,将其中157例足月胎膜早破孕妇设为观察组,另1 097例无胎膜早破孕妇设为对照组,观察分析两组孕妇分娩方案(剖宫产、阴道自娩、阴道助产)与母婴结局(产后出血、胎盘早剥、绒毛膜羊膜炎、伤口愈合不良、产褥病率、胎儿早产、胎儿窘迫、胎粪吸入性肺炎、1 min及5 min的Apgar评分)情况。结果观察组孕妇的剖宫产率为43.9%,明显低于对照组的57.0%,阴道自产率和阴道助产率分别为52.9%和3.2%,均明显高于对照组的42.8%和0.2%,差异均具有统计学意义(P<0.05);观察组孕妇产后出血、胎盘早剥、绒毛膜羊膜炎、伤口愈合不良的发生率分别为6.4%、9.6%、8.9%、3.8%,均明显高于对照组的3.4%、3.3%、3.5%、2.5%,差异均具有统计学意义(P<0.05);观察组孕妇胎儿早产、胎儿窘迫、胎粪吸入性肺炎发生率分别为8.3%、4.5%、4.5%,均明显高于对照组的3.3%、1.9%、2.1%,差异均具有统计学意义(P<0.05);两组孕妇产褥病率、新生儿1 min及5 min的Apgar评分比较差异均无统计学意义(P>0.05)。结论足月胎膜早破孕妇的产道自产与产道助产的几率明显提高,其不良的母婴结局主要体现在产后出血、产妇并发症以及新生儿的并发症方面。

围产期母体营养状态对子代下丘脑食欲调控网络胚胎编程的研究进展

围产期的不良营养因素对子代相关组织的发育具有程控作用,可能引起能量代谢异常并导致代谢相关性疾病的发病。下丘脑是各种食欲调节信号的主要整合中枢,目前已发现多种食欲调节肽在下丘脑食欲调节网络中都扮演了重要的角色。研究表明,下丘脑的食欲调节网络在出生前就已建立,孕晚期及断奶前是食欲调控神经系统的分化发育的关键时期。食欲的调控是一个复杂的生理过程,多种递质、调质或肽类物质参与介导这一机制。其中,脂肪细胞释放的瘦素(leptin)是调控食欲和能量代谢的重要因子。Leptin在围产期母体肥胖程控子代肥胖及代谢异常中可能同样扮演着重要角色,下丘脑食欲调控神经网络的正常发育也一定程度地依赖于出生早期leptin水平的迅速升高。下丘脑的多个脑区,包括摄食调控中枢神经元均表达瘦素受体。研究围产期营养状态对子代下丘脑leptin神经调控网络发育的胚胎编程作用对揭示代谢性疾病发病的先天因素具有重要意义。

宫内慢性缺氧对子代大鼠血管内皮功能的影响

目的探讨胎儿宫内慢性缺氧对子代成年期血管内皮功能的影响及其与性别、高脂血症和再缺氧的关系。方法采用四因素两水平析因设计,研究宫内慢性缺氧、性别、高脂血症、成年期再缺氧对血管内皮依赖性舒张功能的影响。建立大鼠宫内慢性缺氧模型、高脂血症模型与成年期再缺氧模型,观测大鼠血管内皮依赖性舒张功能以及动脉内皮形态学改变。结果除性别因素外,宫内缺氧、高脂血症和再缺氧三个因素均可引起内皮依赖性舒张功能减退(均P<0.01),其主效应分别为14.1%、14.2%和12.9%,其中宫内缺氧与高脂血症对血管内皮功能的影响存在协同交互作用(F=4.889,P<0.05),其余因素之间不存在显著性交互作用。宫内缺氧组部分内皮细胞水肿、坏死、甚至脱落,局部血小板堆积微血栓形成,内皮下层水肿,偶见炎症细胞浸润;正常对照组动脉内皮细胞层结构完整,未见上述改变。结论慢性宫内缺氧可引起子代成年期血管内皮功能与结构的损害,其作用强度与高脂血症、成年期缺氧相近,且可与高脂血症协同促进血管内皮损伤。

基于改进动态规划的雷达弱小目标检测与跟踪

针对复杂背景下雷达弱小目标的检测和跟踪问题,提出了一种改进动态规划的检测前跟踪算法。该方法用多级检验判决方法代替常用的两级门限检测,并用传统跟踪技术进行目标位置状态估计,根据估计值与状态值的欧氏距离设计一个惩罚项来改进值函数。通过仿真验证,结果表明该方法能有效消除伪航迹,减小计算量,提高对雷达弱小目标的检测和跟踪性能。