Effect of curcumin on expressions of NF-κBp65,TNF-αand IL-8 in placental tissue of premature birth of infected mice

Objective:To observe the effect of curcumin on expressions of nuclear transcription factorkappa Bp65(NF-κBp65),TNF--α and IL-8 in placental tissue of premature birth of infected mice induced by lipopolysaccharide(LPS).Methods:A total of 60 C57BL/6 mice pregnant with 15 d were collected and randomly divided into control group,model group,treatment group and preventative group.LPS was repeatedly injected in abdominal cavity to construct infected premature birth model,while mice of control group were given with 100 mg/kg of vitamin C through abdominal cavity injection and mice of treatment group and preventative group were given curcumin of 100 mg/kg through abdominal cavity injection after modeling operation and before 1 d of modeling operation,respectively.A total of 5 mice of four groups respectively were executed by cervical dislocation after 6 h,12 h and 24 h after constructing model.Placental tissues were collected and the immunohistochemical mothod SABC of immunologic tissue was used to detect the expression of NF-d mice after 24 h was collected tκBp65,TNF-o detect the co-and IL-8 and peripheral blood of executencentrations of IL-8,malondialdehyde(MDA) and superoxide dismutase(SOD),meanwhile live birth rate of four groups was contrasted.Results:Staining intensity of NF-tissue of treatment group and preventative group was κBp65,TNF-significantly-αand IL-8 in placental higher than control group but lower than model group(P<0.05).Level of serum IL-8 and MDA of control group was significantly lower than the other three groups(P<0.05) and level of blood of SOD in model group was significantly lower than control group(P<0.05).Levels of serum IL-8 and MDA of treatment group and preventative group were significantly lower than model group(P<0.05) while level of SOD was significantly higher than model group(P<0.05).Live birth rate of treatment group and preventative group was significantly higher than model group(P<0.05).Conclusions:Curcumin can effectively prevent the active pathway of NF-t tissue of premature birth of infected mice,reduce the expression of TNF-κB in pregnanieve the damage of lipid peroxide of oxidative stress of LPS on mother-fetus-α and IL-8 and rel and further to achieve the objective of preventing and curing premature birth induced with infection.

The Indonesian version of the Premature Infant Pain Profile-Revised:Translation and adaptation of a neonatal pain assessment

Purpose: Pain assessment is a key component of good pain management in hospitalized infants.This study aimed to translate and adapt a version of pain measurement in infants,the Premature Infant Pain Profile Revised (PIPP-R) into Indonesian.Method: The adaptation process of the measuring instrument used a modified Brislin method which included forward translation,back translation 1,group discussion 1,back translation 2,group discussion 2,and pilot testing on neonatal nurses: feasibility test,inter-rater reliability using intraclass correlation (ICC),and internal consistency using Cronbach's α coefficient.Results: The PIPP-R version in English has been translated into Indonesian.In general,nurses assessed this measuring instrument as feasible.The inter-rater reliability showed a high agreement (ICC =0.968,P=0.001) and this measuring instrument had good internal consistency (Cronbach's α=0.856).Conclusion: The Indonesian version of PIPP-R is easy to use and shows good psychometric properties.The use of this measuring instrument will help nurses and researchers obtain accurate infant pain intensity measurement values.

Negative regulation of miRNA-9 on oligodendrocyte lineage gene 1 during hypoxic-ischemic brain damage

Oligodendrocyte lineage gene 1 plays a key role in hypoxic-ischemic brain damage and myelin repair, miRNA-9 is involved in the occurrence of many related neurological disorders. Bioin- formatics analysis demonstrated that miRNA-9 complementarily, but incompletely, bound oligodendrocyte lineage gene 1, but whether miRNA-9 regulates oligodendrocyte lineage gene 1 remains poorly understood. Whole brain slices of 3-day-old Sprague-Dawley rats were cultured and divided into four groups： control group; oxygen-glucose deprivation group （treatment with 8% O2 ＋ 92% N2 and sugar-free medium for 60 minutes）; transfection control group （after oxygen and glucose deprivation for 60 minutes, transfected with control plasmid） and miRNA-9 transfection group （after oxygen and glucose deprivation for 60 minutes, transfected with miRNA-9 plasmid）. From the third day of transfection, and with increasing culture days, oligodendrocyte lineage gene 1 expression increased in each group, peaked at 14 days, and then decreased at 21 days. Real-time quantitative PCR results, however, demonstrated that oligoden- drocyte lineage gene 1 expression was lower in the miRNA-9 transfection group than that in the transfection control group at 1, 3, 7, 14, 21 and 28 days after transfection. Results suggested that miRNA-9 possibly negatively regulated oligodendrocyte lineage gene 1 in brain tissues during hypoxic-ischemic brain damage.

Using the Delphi Technique to Achieve Consensus on Prevention and Treatment of Preterm Single Birth in China

Objective::This study aimed to reach a consensus among obstetric experts on the prevention and treatment of preterm single births in China.Methods::Based on the scoping literature review and the 2014 edition of preterm birth of Clinical Diagnosis and Treatment guidelines,we generated the Delphi survey statements with five evaluation dimensions,including the definition of preterm birth,exclusion of risk factors for preterm birth,prevention,and prediction of preterm birth,treatment of preterm birth,and evaluation of intervention outcomes of preterm birth.Obstetric experts from the Obstetrics and Gynecology Branch of the Chinese Medical Association formed the expert group for this survey.All the obstetric experts participated two-round modified Delphi survey via an anonymous online survey and an online panel.Mean scores,rank sum,full score ratio,and the lowest score ratio were calculated to reflect the concentration of expert opinions.The coefficient of variation and Kendall W coefficient were used to reflect the expert opinion coordination degree of the survey statement.Results::The expert response rate for both rounds of surveys was 100%(41/41).Experts reached an agreement on 36 statements in five dimensions of preterm birth prevention and treatment in the first round of the survey and reached a consensus on the remaining 13 statements in the second round.A total of 49 statements(mean scores≥3,full score ratio≥20%,coefficient of variation≤0.3)were explicitly included in this guideline to form recommendations,while the remaining three clinical issues that did not reach a consensus require further determination based on evidence quality.The Kendall W coefficient in the two rounds of the Delphi survey were 0.20(P<0.001)and 0.29(P<0.001).Conclusion::The five dimensions and 49 statements,agreed upon through a two-round Delphi study,determined the recommended statements to be included in the updated guidelines for the prevention and treatment of preterm birth in China.The defined lower limit is set at≥28 gestational weeks;however,an update has been made to the definition of premature birth,specifying that"with the consent of the mother and her family,treatment is not abandoned for viable infants≥26 gestational weeks."

Spontaneous Preterm Birth:a Fetal-Maternal Metabolic Imbalance

Preterm delivery is a major global health problem associated with increased neonatal morbidity and mortality.To develop effective strategies to reduce preterm birth,it is important to address the causes of and risk factors for this condition.Maternal metabolism plays a crucial role in pregnancy outcomes,as it affects the availability of nutrients,energy,and other essential factors required for fetal development and growth.Several aspects of maternal metabolism can potentially contribute to the risk of preterm delivery.Severe energy deficiency as observed in women suffering from eating disorders can affect the hypothalamic-pituitary-gonadal axis resulting in amenorrhea and infertility,suggesting that maintaining a minimum maternal weight is essential to uphold a functional reproductive system,thus ensuring a successful pregnancy.Maternal undernutrition as observed in past famine and observations and animal studies may affect fetal growth and trigger an early activation of the parturition pathway leading to preterm delivery.A correlation exists between maternal size and gestation duration.Obesity is associated with a higher likelihood of medically indicated preterm birth.Low maternal body mass index and low gestational weight gain during pregnancy have been associated with preterm birth,potentially due to fetal-maternal metabolic imbalance;however,the exact mechanism remains to be determined,thus emphasizing the importance of appropriate weight management before and during pregnancy.Addressing metabolic-related risk factors for preterm delivery requires a comprehensive approach to reduce the burden of preterm delivery and improve neonatal outcomes.This review aims to explore various aspects of fetal-maternal metabolic imbalance that could potentially contribute to preterm birth.By doing so,we suggest a novel and comprehensive approach that sheds light on the intricate connection between fetal-maternal imbalance and the susceptibility to preterm birth.

Factors of Fetal Origin in the Regulation of Labor Initiation and Preterm Birth

Preterm birth is the leading cause of mortality and morbidity in newborns and children under 5 years-of-age.In order to improve the survival rate and quality of preterm infants,there is critical need to identify the specific mechanisms underlying the initiation of labor.Pregnancy represents a period of constant interactive dialog between mother and fetus.A disturbance in the pattern of maternal-fetal communication can induce physiological or pathological labor.Although a number of studies have investigated the contributions of maternal factors to the initiation of labor,the concept that fetal organ development and maternal adaptation are coordinated has emerged over recent years,thus emphasizing that factors of fetal origin may serve as hormonal signals for the initiation of labor.In this review,we summarize and discuss several specific mechanisms by which factors of fetal origin may influence parturition during term or preterm labor,including the specific regulation of fetal organs,including the lungs and accessory organs during pregnancy.Future research may focus on the specific pathways by which signals from the fetal lungs and other fetal organs interact with the maternal system to initiate eventual labor.

Predicting the Risk of Preterm Birth Throughout Pregnancy Based on a Novel Transcriptomic Signature

Objective::This study focused on the prediction of preterm birth(PTB).It aimed to identify the transcriptomic signature essential for the occurrence of PTB and evaluate its predictive value in early,mid,and late pregnancy and in women with threatened preterm labor(TPTL).Methods::Blood transcriptome data of pregnant women were obtained from the Gene Expression Omnibus database.The activity of biological signatures was assessed using gene set enrichment analysis and single-sample gene set enrichment analysis.The correlation among molecules in the interleukin 6(IL6)signature and between IL6 signaling activity and the gestational week of delivery and latent period were evaluated by Pearson correlation analysis.The effects of molecules associated with the IL6 signature were fitted using logistic regression analysis;the predictive value of both the IL6 signature and IL6 alone were evaluated using receiver operating characteristic curves and pregnancy maintenance probability was assessed using Kaplan-Meier analysis.Differential analysis was performed using the DEseq2 and limma algorithms.Results::Circulatory IL6 signaling activity increased significantly in cases with preterm labor than in those with term pregnancies(normalized enrichment score(NES)=1.857,P=0.001).The IL6 signature(on which IL6 signaling is based)was subsequently considered as the candidate biomarker for PTB.The area under the curve(AUC)values for PTB prediction(using the IL6 signature)in early,mid,and late pregnancy were 0.810,0.695,and 0.779,respectively;these values were considerably higher than those for IL6 alone.In addition,the pregnancy curves of women with abnormal IL6 signature differed significantly from those with normal signature.In pregnant women who eventually had preterm deliveries,circulatory IL6 signaling activity was lower in early pregnancy(NES=-1.420,P=0.031)and higher than normal in mid(NES=1.671,P=0.002)and late pregnancy(NES=2.350,P<0.001).In women with TPTL,the AUC values for PTB prediction(or PTB within 7 days and 48 hours)using the IL6 signature were 0.761,0.829,and 0.836,respectively;the up-regulation of IL6 signaling activity and its correlation with the gestational week of delivery(r=-0.260,P=0.001)and latency period(r=-0.203,P=0.012)were more significant than in other women.Conclusion::Our findings suggest that the IL6 signature may predict PTB,even in early pregnancy(although the predictive power is relatively weak in mid pregnancy)and is particularly effective in symptomatic women.These findings may contribute to the development of an effective predictive and monitoring system for PTB,thereby reducing maternal and fetal risk.

Mechanisms of Immune Tolerance and Inflammation via Gonadal Steroid Hormones in Preterm Birth

In 2019,preterm births(PTB)accounted for approximately 0.66 million deaths globally.PTB is also associated with a significantly higher risk of mortality and long-term complications for newborns.Long-term studies associated several factors,including disruption of immune tolerance and inflammation,with PTB.However,the pathogenesis of PTB remains unclear.Gonadal steroid hormones are critical for pregnancy maintenance and regulation of immune and inflammatory responses.However,it is not clear how unbalanced gonadal steroid hormones,such as imbalanced estrogen/androgen or estrogen/progesterone contribute to PTB.In this review,we discuss how gonadal steroid hormones mediate dysfunction in immune tolerance and inflammatory responses,which are known to promote the occurrence of PTB,and provide insight into PTB prediction.

Analysis of Clinical Differences Between Preterm Delivery and Full-Term Delivery among Pregnant Women with Gestational Diabetes Mellitus

Objective:To investigate the clinical characteristics of preterm delivery and full-term delivery in pregnant women with gestational diabetes mellitus(GDM).Methods:Women who were diagnosed with GDM by 75 g glucose tolerance test(OGTT)between 24 and 28 weeks of gestation were selected as the subjects of the study.According to the delivery time,they were divided into full-term group(n=61)and preterm group(n=42).Results:There was no statistical difference in the puerpera between preterm group and full-term group(P>0.05).The incidence of hyperhydramnios and oligohydramnios in the term group was 16.19%and 2.38%,respectively.The number of hyperhydramnios and oligohydramnios in the full-term group was lower than that in the preterm group,and the difference was statistically significant(P<0.05).Conclusion:Prolonged gestation period can effectively reduce the incidence of polyhydramnios and oligohydramnios,and prevent premature delivery,improve the quality of blood glucose management in diabetic patients,avoid hypoglycemia and other complications,and reduce the threat to the life of pregnant women and the fetus.

Effect of Tuina on Neurodevelopment in Premature Infants with Brain Injury

Objective： To investigate the effect of tuina on promoting neurodevelopment of premature infants with brain injury. Methods： A total of 82 cases who met the inclusion criteria were randomized into an intervention group and a control group. In addition to early conventional intervention （Chinese medicinal bath therapy and physical training）, specific tuina manipulations （aims to unblock the Governor Vessel, refresh the brain, benefit the kidney and strengthen the spleen） were combined in the intervention group, whereas comforting touch in the control group. The rehabilitation assessments were then made prior to treatment and three months after the treatment using Gross Motor Function Measure （GMFM）, Bayley Scales of Infant Development-II （BSID-II） and Gesell Developmental Schedules （GDS） based Developmental Quotient （DQ）. Results： The DQ in all GDS areas and scores of GMFM A and B dimensions were significantly increased in both groups after the treatment （P〈0.01）. The DQ and population mean of GMFM B dimension in the intervention group were higher than those in the control group, showing statistical differences （P〈0.05）. However, in terms of Mental Development Index （MDI） and Physical Development Index （PDI） in both groups, there were no statistical differences before and after treatments. Conclusion： Both methods combined with conventional early intervention can help to improve the mental and motor development of infants with brain injury. However, the specific tuina manipulations have been proved more effective in improving the infants＇ gross motor function, particularly the ＂sitting＂ item.

Cervical Assessment by Transvaginal Ultrasound for Predicting Preterm Birth in Asymptomatic Women

Preterm birth(PTB)is defined as delivery before completing 37 weeks of gestation.It is the main cause of neonatal morbidity and mortality in the most countries.The inherent cervical length and strength are two main features of the cervix that determine whether or not a pregnant woman is at risk for PTB.Routine transvaginal cervical length screening was recommended for women with singleton pregnancy and history of prior spontaneous PTB,while the issue of universal cervical length screening and the screening in multiple gestations remain an object of debate.Strain sonoelastography and shear-wave sonoelastography have been used to evaluate the cervical stiffness in pregnant women,but the predictive value for PTB still requires further investigations.In this review,we will discuss the measurement methods of cervical length and cervical stiffness,and compare the value of cervical assessment by transvaginal ultrasound for predicting PTB in asymptomatic women.

Preterm Birth,From the Biological Knowledges to the Prevention:An Overview

The time of birth is a critical determinant of perinatal and long-term outcomes,and even trans-generational effects.Preterm birth is still the leading cause of infant mortality and morbidity.Unfortunately,rates of preterm birth remain high worldwide.Preterm parturition is a complex syndrome,which can be induced by several factors such as infection,cervical pathology,uterine overdistension,progesterone deficiency,vascular alterations(utero-placental ischemia,decidual hemorrhage),maternal and fetal stress,allograft reaction,allergic phenomena,and probably other several unknown factors.The mechanisms responsible for early labor activation have been partially identified and involve receptors,chemokines,and inflammatory cytokines.It is very useful to understand the cellular and biochemical pathways responsible for preterm labor activation to identify,treat,and prevent negative outcome in a timely manner.Researchers and clinicians play a key role in improving biochemical knowledge on preterm delivery,identifying risk factors,and applying multilevel preventive strategies.

Retinopathy of prematurity： an epidemic in the making

Objective To explore the etiology, incidence and methods to prevent and treat severe retinopathy of prematurity （ROP）,which is rapidly becoming a threat to the vision of babies in areas of the world where increasing numbers of premature babies are surviving.Data sources The data used in this review were mainly from Medline and PubMed published in English. The search term was ＂retinopathy of prematurity and premature birth＂.Study selection We discuss the historical perspectives, prevalence and incidence, classification and treatment methods of ROP in premature babies.Results Peripheral retinal ablation for eyes with severe ROP can help prevent progression to blindness and several large clinical trials have shown the effectiveness of this treatment in high risk eyes. As a greater proportion of VLBW and ELBW babies survive, the population of babies at risk increases. In various regions of the world, different identification criteria are used to determine which babies are at risk of blindness in order to provide timely diagnostic examinations and treatment as needed. Methods for preventiing ROP include better ante-natal and obstetric care leading to a reduction in the rate of prematurity, the use of ante-natal corticosteroids, and better neonatal care practices. Recent developments have indicated that management of oxygen supplementation is important for the prevention of severe ROP; however,there is not yet known what oxygen saturation target should be adopted. Sepsis increases severe ROP in very preterm infants. Genetic associations and a telemedicine approach may be explored to detect ROP. Treatment of anti-VEGF therapy are potentially useful in eyes with severe ROP, but long term effects are not yet known and such treatment should be used with great caution.Conclusions ROP is a potentially binding disease for premature babies which is becoming more prevalent with the development improving neonatal services in many countries in recent years. High priority should be placed on developing approaches to prevent ROP blindness by reducing preterm birth, improving care of premature babies in neonatal care units, and providing adequate ophthalmological services in those regions.

Obstetric Outcomes in Chinese Women with Endometriosis： A Retrospective Cohort Study

Background：The effect of endometriosis on obstetric outcomes is still ambiguous.The aim of our study was to determine the association between endometriosis and adverse obstetric outcomes in a cohort of Chinese women.Methods：A retrospective cohort study was undertaken to compare obstetric outcomes between 249 women with endometriosis and 249 women without endometriosis.All women were nulliparous and achieved singleton pregnancies naturally.Women with endometriosis were diagnosed during surgery and confirmed histologically.Odds ratios （ORs） and 95％ confidence intervals （CIs） of measures of obstetric outcomes were calculated.Results：Women with endometriosis showed significantly increased risks of preterm labor （adjusted OR,2.42; 95％ CI,1.05-5.57）,placenta previa （adjusted OR,4.51; 95％ CI,1.23-16.50）,and cesarean section （adjusted OR,1.93; 95％ CI,1.31-2.84）.No significant differences were observed in the incidence of pregnancy-induced hypertension,fetal growth restriction,small for gestational age,placental abruption,or luteal support in the first trimester between the two groups.Conclusions：Women with endometriosis are at a higher risk of preterm labor,placenta previa,and cesarean section during pregnancy and need additional care.

Characterization of a recombinant Akabane mutant virus with knockout of a nonstructural protein NSs in a pregnant goat model

Dear Editor,Akabane virus(AKAV),an orthobunyavirus,is transmitted primarily by biting midges and is widely distributed throughout the world except the Europe.AKAV was first isolated from mosquitoes in Japan(Oya et al.,1961).Although pregnant cows,ewes,and goats infected with AKAV exhibit no clinical signs of disease,in utero infections result in abortion,premature birth,stillbirth。

Highlights from the International Twins Congress 2021

Toeditor:The Twins Congress(TC)2021 took place in Beijing(China)from June 4-6,2021.The TC was organized jointly with the International Society for Twin Studies and held in conjunction with the Fifth Joint World Congress on Twin Pregnancy.This was the first time the TC had been held in Asia.The TC was chaired by professors Gian Carlo Di Renzo(ltaly),Jeffrey Craig(Australia),Asma Khalil(United Kingdom),and Ruben Quintero(United States).The local host was Professor Huixia Yang.Other members of the International Advisory Committee included professors Liona Poon(Hong Kong SAR,China),Jose Luis Bartha(Spain),Roberto Romero(United States),Gerard H.A.Visser(the Netherlands),and Tak Yeung Leung(Hong Kong SAR,China).