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Abstract To explore the associations between high uterine artery pulsatility index (UtA-PI) values and congenital heart disease (CHD) risk and whether they differed between singleton and multiple pregnancies. This hospital-based cohort study involving 52,047 pregnant women who underwent prenatal examinations from 2012 to 2016. Infants born to the included pregnant women were followed until 42 days after birth to identify those with CHDs. Generalized estimating equations were used to estimate the associations of high right UtA-PI (> 95th percentile) values with maternal preeclampsia and fetal CHDs. Logistic regression analyses were conducted using path analysis models to quantify the effect of high right UtA-PI values on fetal CHD risk. A total of 42,552 women and 43,470 infants (147 with CHDs) were included. Preeclampsia risk was associated with a high right UtA-PI in singleton-pregnant women (adjusted PR, 3.01; 95% CI 2.57–3.52). CHD risk was marginally associated with a high right UtA-PI in singleton-pregnant women (adjusted PR, 2.26, 95% CI 1.03–4.95). Considering only two factors, 96.0% of the fetal CHD risk was mediated by preeclampsia in singleton-pregnant women, while 93.8% of the risk was related to a high right UtA-PI in multiple-pregnant women. A high right UtA-PI was marginally associated with an increased fetal CHD risk in singleton-pregnant women and might play an important role in multiple-pregnant women. Further studies are warranted to confirm these findings given the high loss to follow-up rate.

Abstract Background Vitamin D deficiency is common among the population, but its relationship with mortality of postmenopausal females is unclear. The aim of this study is to explore the association between serum 25-Hydroxyvitamin D (25(OH)D) and all-cause and cause-specific mortality among postmenopausal women in the United States. Methods 6812 participants of postmenopausal females from the National Health and Nutrition Examination Survey (2001–2018) were included in this study. The mortality status of the follow-up was ascertained by linkage to National Death Index (NDI) records through 31 December 2019. We used cox proportional hazards models to estimate the association of serum 25(OH)D concentrations and mortality of postmenopausal females. Results The mean level of serum 25(OH)D was 72.57 ± 29.93 nmol/L, and 65.34% had insufficient vitamin D. In postmenopausal females, low serum 25(OH)D concentrations were significantly associated with higher levels of glycohemoglobin, glucose, and lower levels of HDL. During follow-up, 1448 all-cause deaths occurred, including 393 cardiovascular disease (CVD)-related deaths and 263 cancer deaths. After multivariate adjustment, higher serum 25(OH)D levels were significantly related with lower all-cause and CVD mortality. In addition, serum 25(OH)D presented a L-shaped relationship with all-cause mortality, while appeared a U-shaped with CVD mortality, and the cut-off value is 73.89 nmol/L and 46.75 nmol/L respectively. Conclusions Low serum 25(OH)D levels are associated with the higher risk of all-cause and CVD mortality in postmenopausal females. These findings provide new ideas and targets for the health management of postmenopausal women.

Abstract Background Folic acid (FA) supplementation is associated with a lower risk of the neural tube and heart defects and is recommended for women of childbearing age. Although there are detailed recommendations, differences in the initiation time and duration of FA supplementation remain poorly studied. Methods A multicentre prospective study of 17,713 women was conducted. The incidence of congenital malformations in women taking a recommended dosage (e.g. 0.4 or 0.8 mg/day) of FA was compared with that in women without supplementation. The predicted probability of malformations by the initiation time and duration of FA use was estimated to determine optimal options. Results Periconceptional FA supplementation was associated with a lower and insignificant risk of congenital malformations (1.59% vs. 2.37%; odds ratio [OR] 0.69; 95% confidence interval [CI]: 0.44–1.08), heart defects (3.8 vs. 8.0 per 1000 infants; OR, 0.47; 0.21–1.02), and neural tube defects (7.0 vs. 11.5 per 10,000 infants; OR, 0.64; 0.08–5.15). FA use after pregnancy provided greater protection against total malformations. Statistically significant associations were found in women who initiated FA supplementation in the first month of gestation (OR, 0.55; 95% CI: 0.33–0.91) and in those who supplemented for 1 to 2 months (OR, 0.59; 95% CI: 0.36–0.98). Similar results were found for heart defects. The optimal initiation time was 1.5 (optimal range: 1.1 to 1.9) months before pregnancy and a duration of 4.0 (3.7 to 4.4) months was reasonable to achieve the lowest risk of congenital malformations. Heart defect prevention required an earlier initiation (2.2 vs. 1.1 months before pregnancy) and a longer duration (4.7 vs. 3.7 months) than the prevention of other malformations. Conclusions The timely initiation of FA supplementation for gestation was associated with a decreased risk of congenital malformations, which was mainly attributed to its protection against heart defects. The initiation of FA supplementation 1.5 months before conception with a duration of 4 months is the preferred option for congenital malformation prevention. Trial registration Chictr.org.cn identifier: ChiCTR-SOC-17010976.

Abstract Background Female offspring was associated with a high risk of postpartum depression (PPD) during the one-child policy period in China. However, little is known about the association between maternal expectations on fetal gender and the risk of PPD in the context of the new two children policy implemented in 2016. Methods We conducted a hospital-based cohort study of women with singleton pregnancies between 2017 and 2018 (n = 991) to address this concern. Logistic regression was run to estimate the association between unexpected fetal gender and the risk of PPD. Results A total of 127 women (12.8%) were diagnosed with PPD. Compared with women who achieved fetal gender expectations, the odds ratio (OR) for PPD among those who had an unexpected fetal gender was 2.44 (95% confidence interval (CI): 1.30–4.58) (in the backward method logistic regression model) and 2.25 (95% CI: 1.21–4.18) (in the forward method model), respectively. The disparity of the association was significant among primiparous and pluriparous women (OR, 2.52, 95% CI: 1.32–4.84, P = 0.005 vs. OR, 0.91, 95% CI: 0.09–8.75, P = 0.932). Fetal gender expectations accounted for about 15% of the risk of PPD in the structural equation models. Conclusions These results indicated that unexpected fetal gender was associated with an increased risk of PPD among Chinese primiparous women.

Abstract Background Evidence for the association of thyroid dysfunction and autoantibody positivity with preterm birth remains controversial. We aimed to study the association of maternal thyroid dysfunction and autoantibody positivity with the risk of preterm birth. Method A hospital-based cohort study of 40,214 women was conducted. Gestational age-specific percentiles of the FT4 and TSH concentrations were used for the definition of thyroid dysfunction. Autoantibody positivity was identified when the concentration > the threshold. The association of thyroid dysfunction and autoantibody positivity with the risk of preterm birth was estimated. Results No significant higher risk of preterm birth was found for women with variants of thyroid dysfunction or autoantibody positive than euthyroid women. Sensitivity and stratification analyses indicated that thyroperoxidase antibody (TPOAb) positivity in the first trimester (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.17–1.90) and overt hypothyroidism restricted to women negative for TPOAb (OR, 4.94; 95%CI: 1.64–14.84) was associated with an increased risk of preterm birth. Modification effects of gestational age were found for women who had the test ≤18 and > 18 weeks. Continuous FT4 measurements tested ≤18 weeks of gestation were associated with a higher risk of preterm birth (OR, 1.13, 95% CI: 1.00–1.28), while a negative relationship for FT4 concentrations tested > 18 weeks of gestation (OR = 0.68, 95% CI: 0.48–0.97). Conclusions Some specific thyroid function abnormalities were associated with an increased risk of preterm birth. Interaction between gestational age and FT4 concentration on the risk of preterm birth was identified, with a critical node of 18 weeks of gestation.

Abstract Background Plenty of studies explored the relationship between uterine artery (UtA) Doppler indices and the onset of preeclampsia at different trimesters. However, few studies test the gestational week-specific predictive value of the UtA indices for subsequent preeclampsia and compare the difference of right or left UtA indices (e.g., pulsatility or resistance index [PI or RI]). Methods Hospital-based retrospective cohort study of singleton pregnant women who received the Doppler test between 2012 and 2016 was conducted in 2018. The predictive performance of the UtA indices for preeclampsia and its variants, including early-onset preeclampsia (

IntroductionRecurrent implantation failure (RIF) is a frustrating challenge because the cause is unknown. The current study aims to identify differentially expressed genes (DEGs) in the endometrium on the basis of immune cell infiltration characteristics between RIF patients and healthy controls, as well as to investigate potential prognostic markers in RIF.MethodsGSE103465, and GSE111974 datasets from the Gene Expression Omnibus database were obtained to screen DEGs between RIF and control groups. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes Pathway analysis, Gene Set Enrichment Analysis, and Protein-protein interactions analysis were performed to investigate potential biological functions and signaling pathways. CIBERSORT was used to describe the level of immune infiltration in RIF, and flow cytometry was used to confirm the top two most abundant immune cells detected.Results122 downregulated and 66 upregulated DEGs were obtained between RIF and control groups. Six immune-related hub genes were discovered, which were involved in Wnt/-catenin signaling and Notch signaling as a result of our research. The ROC curves revealed that three of the six identified genes (AKT1, PSMB8, and PSMD10) had potential diagnostic values for RIF. Finally, we used cMap analysis to identify potential therapeutic or induced compounds for RIF, among which fulvestrant (estrogen receptor antagonist), bisindolylmaleimide-ix (CDK and PKC inhibitor), and JNK-9L (JNK inhibitor) were thought to influence the pathogenic process of RIF. Furthermore, our findings revealed the level of immune infiltration in RIF by highlighting three signaling pathways (Wnt/-catenin signaling, Notch signaling, and immune response) and three potential diagnostic DEGs (AKT1, PSMB8, and PSMD10).ConclusionImportantly, our findings may contribute to the scientific basis for several potential therapeutic agents to improve endometrial receptivity.

China has regulated its hepatitis B vaccination policy. However, data on the prevalence of hepatitis B virus (HBV) infection have not been updated since 2014. In addition, the impact of the policy on awareness of hepatitis B is limited, especially in Fujian Province where HBV infection is highly prevalent. We conducted a sero-epidemiological survey in five national monitoring counties to address these concerns. A total of 5,873 subjects were included and classified into four birth cohorts according to the policy time nodes (1981, 1992, and 2002). The HBsAg carrier rate for the general population was 8.6% (95% confidence interval [CI]: 7.9–9.3). Compared with those born before 1981, adjusted odds ratios (OR) for HBV infection were 0.51 (95% CI: 0.43–0.62), 0.10 (0.08–0.12), and 0.015 (0.01–0.023) among the 1981–1991, 1992–2001, and ≥2002 birth cohorts, respectively; while the OR was 1.26 (1.00–1.57), 0.39 (0.26–0.58), and 0.019 (0.006–0.06) for HBsAg carriage, respectively. Among the 4865 residents aged ≥15 years, hepatitis B awareness has been declining since the introduction of the hepatitis B vaccine into the immunization program (β = −0.25, SE = 0.08, P = .001, and β = −0.20, SE = 0.08, P = .017 for 1992–2001 and ≥2002 birth cohort, respectively). This decline was obvious for the initiation time of the first dose of the hepatitis B vaccine. Although the hepatitis B vaccination policies have helped reduce the infection, the awareness has declined. More measures on the target population are warranted to improve the public’s awareness of hepatitis B vaccination in the context of great achievements.

The increased dose of hepatitis B vaccine has been adopted for newborns since 2013 in Fujian, China. However, little is known about the impact of this measure on hepatitis B virus (HBV) prevention. We used the seroepidemiological surveys conducted in 2014 and 2020 to address the concern. Compared with subjects who received a 5 μg hepatitis B vaccine, participants who took a 10 μg hepatitis B vaccine were associated with a lower risk of HBV infection (adjusted odds ratio [OR] 0.26, 95% confidence interval [CI]: 0.10–0.68) and a marginal reduction risk of anti-HBc positive (OR, 0.37; 95% CI: 0.13–1.08; P = .07), but not for HBsAg carrier risk. The relation between vaccine dose and risk of anti-HBc positive (OR, 0.20; 95% CI: 0.05–0.81) became slightly stronger and significant among children investigated in 2020 who probably received universal vaccination. No significant association was found for subjects whose mothers were positive for HBsAg. The current 10 μg hepatitis B vaccines for universal vaccination for newborns are reasonable and effective in HBV prevention. More measures should be taken to reduce the risk of HBsAg carriers for infants whose mothers are positive for HBsAg.

Uterine endometrial cancer (UEC) is an estrogen-related tumor. Succinate and heme metabolism play important roles in the progression of multiple tumors. However, the relationship between estrogen, succinate, and heme metabolism and related regulatory mechanisms remain largely unknown. In this study, we observed that the expression of aminolevulinate delta synthase 1 (ALAS1) and solute carrier family member 38 (SLC25A38) in UEC tissues is significantly higher than that in normal tissues. Further analysis showed that estrogen and succinate increased the expression of ALAS1 and SLC25A38 in uterine endometrial cancer cells (UECC), and the administration of succinate upregulated the level of the estrogen receptor (ER). Silencing nuclear receptor coactivator 1 (NCOA1) reversed the effects of estrogen and succinate via downregulation of ALAS1 expression. Additionally, exposure of UECC to heme increased cell viability and invasiveness, while silencing the NCOA1 gene weakened this effect. These findings revealed that estrogen and succinate can synergistically increase the expression of ALAS1 and SLC25A38 via the ERβ/NCOA1 axis, promoting heme accumulation and increasing the proliferative and invasive potential of UECC.

Abstract Background A lack of information on specific and interventional factors for stillbirth has made designing preventive strategies difficult, and the stillbirth rate has declined more slowly than the neonatal death rate. We compared the prevalence of stillbirth among the offspring of women with or without abnormal placental perfusion (APP). Methods We conducted a hospital-based retrospective cohort study involving women with a singleton pregnancy between 2012 and 2016 (N = 41,632). Multivariate analysis was performed to compare the prevalence of stillbirth in infants exposed to APP (defined as any abnormality in right or left uterine artery pulsatility index or resistance index [UtA-PI, −RI] [e.g., > 95th percentile] or presence of early diastolic notching) with that in those not exposed to APP. Results Stillbirths were more common among women with APP than among those with normal placental perfusion (stillbirth rate, 4.3 ‰ vs 0.9 ‰; odds ratio (OR), 4.2; 95% confidence interval (CI), 2.2 to 8.0). The association strengths were consistent across groups of infants exposed to APP that separately defined by abnormality in right or left UtA-PI or -RI (OR ranged from 3.2 to 5.3; all P ≤ 0.008). The associations were slightly stronger for the unexplained stillbirths. Most of the unexplained stillbirth risk was attributed to APP (59.0%), while a foetal sex disparity existed (94.5% for males and 58.0% for females). Women with normal placental perfusion and a male foetus had higher credibility (e.g., higher specificities) in excluding stillbirths than those with APP and a female foetus at any given false negative rate from 1 to 10% (93.4% ~ 94.1% vs. 12.3% ~ 14.0%). Conclusions APP is associated with and accounts for most of the unexplained stillbirth risk. Different mechanisms exist between the sexes. The performance of screening for stillbirth may be improved by stratification according to sex and placental perfusion.

Glucose is of great importance in cancer cellular metabolism. Working together with several glucose transporters (GLUTs), it provides enough energy for biological growth. The main glucose transporters in endometrial cancer (EC) are Class 1 (GLUTs 1–4) and Class 3 (GLUTs 6 and 8), and the overexpression of these GLUTs has been observed. Apart from providing abundant glucose uptake, these highly expressed GLUTs also participate in the activation of many crucial signaling pathways concerning the proliferation, angiogenesis, and metastasis of EC. In addition, overexpressed GLUTs may also cause endometrial cancer cells (ECCs) to be insensitive to hormone therapy or even resistant to radiotherapy and chemoradiotherapy. Therefore, GLUT inhibitors may hopefully become a sensitizer for EC precision-targeted therapies. This review aims to summarize the expression regulation, function, and therapy sensitivity of GLUTs in ECCs, aiming to provide a new clue for better diagnosis and treatment of EC.

Abstract Background Early identification of patients who are at high risk of poor clinical outcomes is of great importance in saving the lives of patients with novel coronavirus disease 2019 (COVID-19) in the context of limited medical resources. Objective To evaluate the value of the neutrophil to lymphocyte ratio (NLR), calculated at hospital admission and in isolation, for the prediction of the subsequent presence of disease progression and serious clinical outcomes (e.g., shock, death). Methods We designed a prospective cohort study of 352 hospitalized patients with COVID-19 between January 9 and February 26, 2020, in Yichang City, Hubei Province. Patients with an NLR equal to or higher than the cutoff value derived from the receiver operating characteristic curve method were classified as the exposed group. The primary outcome was disease deterioration, defined as an increase of the clinical disease severity classification during hospitalization (e.g., moderate to severe/critical; severe to critical). The secondary outcomes were shock and death during the treatment. Results During the follow-up period, 51 (14.5%) patients’ conditions deteriorated, 15 patients (4.3%) had complicated septic shock, and 15 patients (4.3%) died. The NLR was higher in patients with deterioration than in those without deterioration (median: 5.33 vs. 2.14, P 0.80). The sensitivity of an NLR ≥ 2.6937 for predicting subsequent disease deterioration, shock and death was 82.0% (95% confidence interval, 69.0 to 91.0), 93.3% (68.0 to 100), and 92.9% (66.0 to 100), and the corresponding negative predictive values were 95.7% (93.0 to 99.2), 99.5% (98.6 to 100) and 99.5% (98.6 to 100), respectively. Conclusions The NLR measured at admission and in isolation can be used to effectively predict the subsequent presence of disease deterioration and serious clinical outcomes in patients with COVID-19.

Abstract Background The effect and extent of abnormal placental perfusion (APP) on the risk of male hypospadias are poorly understood. We compared the prevalence of male hypospadias in the offspring of women with APP and quantify the extent of the APP effect on the anomaly. Methods A hospital-based retrospective analysis of births from 2012 to 2016 was conducted in 2018. Women of singleton pregnancy and male infants born to them were included (N = 21,447). A multivariate analysis was performed to compare the prevalence of male hypospadias in infants exposed to APP with those that were not exposed to APP. Results Compared with the infants of women without APP, infants of women with APP showed an increased risk of male hypospadias (odds ratio, 2.40; 95% confidence interval, 1.09–5.29). The male hypospadias cumulative risk increased with the severity of APP. Infants exposed to severe APP had a significantly higher risk of male hypospadias than those without APP exposure (9.2 versus 1.7 per 1000 infants, P

Background. Evidence for the association between maternal thyroxine concentration and the risk of fetal congenital heart defects (CHDs) is absent. We aimed to study the association of maternal free and total thyroxine (FT4 and TT4) concentrations and the free-to-total thyroxine proportion (FTT4P, %) with the risk of CHD. Methods. The study was a hospital-based cohort study of 52,047 women who received a universal thyroid function test between 2012 and 2016. CHD was screened by ultrasound between 20 and 24 weeks of gestation or diagnosed until the 42nd day of birth. Adjusted odds ratios (ORs) of fetal CHD were estimated for maternal FT4 and TT4 concentrations or the FTT4P by multivariate logistic regression. Results. A total of 41,647 women with singleton pregnancies were included for the analysis and 215 CHD cases were detected. The FT4 concentration was significantly associated with a higher risk of CHDs (OR, 1.04, 95% confidence interval (CI): 1.01 to 1.07). Each 1% higher FTT4P was related to a 1.41-fold (95% CI: 0.27 to 3.59) higher risk of CHDs. The association became stronger for women with a thyroid function test performed between 12 and 18 weeks of gestation (OR = 1.05 (95% CI: 1.01 to 1.09) for the FT4 concentration and 3.32 (95% CI: 1.43 to 7.73) for the FTT4P). Conclusions. A higher FT4 concentration or FTT4P, measured between 12 and 18 weeks of gestation, was associated with an increased risk of CHDs. These findings may provide new insights into the mechanisms of CHDs and evidence for clinical decisions related to thyroid function tests.

Abstract Background Excessive estrogen exposure is an important pathogenic factor in uterine endometrial cancer (UEC). Recent studies have reported the metabolic properties can influence the progression of UEC. However, the underlying mechanisms have not been fully elucidated. Methods Glutaminase (GLS), MYC and autophagy levels were detected. The biological functions of estrogen-MYC-GLS in UEC cells (UECC) were investigated both in vivo and in vitro. Results Our study showed that estrogen remarkably increased GLS level through up-regulating c-Myc, and enhanced glutamine (Gln) metabolism in estrogen-sensitive UEC cell (UECC), whereas fulvestrant (an ER inhibitor antagonist) could reverse these effects. Estrogen remarkably promoted cell viability and inhibited autophagy of estrogen sensitive UECC. However, CB-839, a potent selective oral bioavailable inhibitor of both splice variants of GLS, negatively regulated Gln metabolism, and inhibited the effects of Gln and estrogen on UECC’s growth and autophagy in vitro and / or in vivo. Conclusions CB-839 triggers autophagy and restricts growth of UEC by suppressing ER/Gln metabolism, which provides new insights into the potential value of CB-839 in clinical treatment of estrogen-related UEC.

Background: An effective method for the rapid identification of vulnerable preschool children at risk of not completing the national immunization programme (NIP) vaccine series in China is still lacking. Methods: A cross-sectional study involving 772 preschool children born between September 1 2009 and August 31, 2011 was conducted in 2015 in Fujian Province, south-eastern China. The data were collected by face-to-face interviews with the parents or guardians of the children using a standard questionnaire. Results: Children who received the first dose of a hepatitis B vaccine (HepB) less than 24 h after birth and those who received one or more doses of surrogate for-fee vaccines (SFVs) were more likely to complete the NIP vaccine series with adjusted odds ratios (ORs) of 3.12 (95% confidence interval [CI]: 1.19–8.23) and 4.74 (1.41–15.90), respectively. The cut-off value of the prediction score for the completion of the NIP vaccine series was 92.5%, and the sensitivity, specificity, and positive and negative predictive values were 87.5%, 47.1%, 11.4% and 98.0%, respectively. Conclusions: The receipt of a timely first dose of HepB and one or more doses of SFVs were associated with and good predictors of NIP vaccine series completion by preschool children in Fujian, China. Keywords: National immunization programme, Screening models, Cross-sectional study

A vaccine booster to maintain high antibody levels and provide effective protection against COVID-19 has been recommended. However, little is known about the safety of a booster for different vaccines. We conducted a parallel controlled prospective study to compare the safety of a booster usingfour common vaccines in China. In total, 320 eligible participants who had received two doses of an inactivated vaccine were equally allocated to receive a booster of the same vaccine (Group A), a different inactivated vaccine (Group B), an adenovirus type-5 vectored vaccine (Group C), or a protein subunit vaccine (Group D). A higher risk of adverse reactions, observed up to 28 days after injection, was found in Groups C and D, compared to Group A, with odds ratios (OR) of 11.63 (95% confidence interval (CI): 4.22–32.05) and 4.38 (1.53–12.56), respectively. Recipients in Group C were more likely to report ≥two reactions (OR = 29.18, 95% CI: 3.70–229.82), and had a higher risk of injection site pain, dizziness, and fatigue. A gender and age disparity in the risk of adverse reactions was identified. Despite the majority of reactions being mild, heterologous booster strategies do increase the risk of adverse reactions, relative to homologous boosters, in subjects who have had two doses of inactive vaccine.

Background: Little is known about the association between the initiation of hepatitis B vaccine (HB vaccine) at birth and completion of the HB vaccine and the national immunization program vaccine (NIPV) series in Fujian, China. Methods: A provincial survey, including children in the community and newborns in hospital, was conducted to evaluate coverage with a timely first dose of HB vaccine and the completion of three doses of HB vaccine and the NIPV series in 2013. A proportion of the samples was rechecked to investigate the relationship between the administration of a timely first dose of HB vaccine and completion of the HB vaccine series and the NIPV series (three doses of HB vaccine, one dose of Bacillus Calmette–Guérin vaccine, three doses of oral poliomyelitis vaccine, three doses of diphtheria–tetanus–pertussis vaccine, one dose of measles-containing vaccine, one dose of Japanese encephalitis attenuated live vaccine, and two doses of group A meningococcal polysaccharide vaccine). Results: A total of 6589 subjects (including 3785 community children and 2804 hospital newborns) were included in this study; 97.34% of them received a timely first dose of HB vaccine (≤24 h after birth) and 99.10% and 88.27% completed the HB vaccine series and the NIPV series, respectively. Among the 1680 children from eight counties who were rechecked, those with a timely first dose of HB vaccine had higher completion rates of the HB vaccine series and the NIPV series than those with a delayed first dose of HB vaccine (99.69% and 88.90% vs. 83.05% and 79.66%, respectively; both p

Introduction: The potential teratogenic risk of traditional Chinese medicine (TCM) is of widespread concern; however, related evidence is largely absent in humans. This study aimed to compare the prevalence of congenital malformations between pregnant women with and without TCM exposure. Material and methods: This was a multicenter prospective cohort study of 17 713 women who participated in a survey on periconceptional TCM exposure. Primary outcome was congenital malformations diagnosed from a survey conducted on the day 42 after delivery. Results: A total of 16 751 pregnant women with 273 congenital malformations were included in the analysis. Fetuses exposed to TCM had an increased risk of congenital malformations compared to those without exposure (odds ratio [OR] 2.10; 95% confidence interval [CI] 1.09-4.02) after controlling for potential confounders. There were significant associations with congenital malformations in women with early pregnant exposure (OR 2.04, 95% CI 1.00-4.20) and for those who received =2 TCM formulas (OR 5.84, 95% CI 1.44-23.65). Pre-pregnancy TCM exposure was significantly associated with an increased risk of congenital heart defects (OR 12.69; 95% CI 3.01-53.51). Conclusions: Periconceptional TCM exposure is associated with an increased risk of congenital malformation. This effect was cumulative and sensitive to periconceptional age. Therefore, TCM deserves more attention and should be used cautiously for pregnant women and those trying to become pregnant. [ABSTRACT FROM AUTHOR]

A successful pregnancy requires sufficient decidualization of endometrial stromal cells (ESCs). CD82, a metastasis suppressor, is a critical regulator for trophoblast invasion but the effect in decidualization was largely unknown. Here we reported that there was a high level of CD82 in DSC by the immunohistochemistry staining and flow cytometer analysis. Stimulation with prostaglandin E2 (PGE2) elevated the expression of CD82 in ESCs. In contrast, celecoxib, a selective COX-2 inhibitor, significantly downregulated the expression of CD82 in decidual stromal cells (DSCs). Bioinformatics analysis and further research showed that recombinant human interleukin (IL)-1ß protein (rhIL-1ß) upregulated CD82 in ESCs. Of note, blocking IL-1ß signaling with anti-human IL-1ß neutralizing antibody could reverse the stimulatory effect of PGE2 on CD82 in ESCs. Silencing CD82 resulted in the decease of the decidualization markers PRL and IGFBP1 mRNA levels in DSCs. More importantly, we observed rhIL-1ß also upregulated the expression of COX-2, and the upregulation of PRL and IGFBP1 induced by rhIL-1ß could be abolished by celecoxib in ESCs or CD82 deficiency in DSCs. This study suggests that CD82 should be a novel promotor for decidualization under a positive regulation of the COX-2/PGE2/IL-1ß positive feedback loop. [ABSTRACT FROM AUTHOR]

The survival and development of a semi-allogeneic fetus during pregnancy require the involvement of decidual stromal cells (DSCs), a series of cytokines and immune cells. Insulin-like growth factor 1 (IGF1) is a low molecular weight peptide hormone with similar metabolic activity and structural characteristics of proinsulin, which exerts its biological effects by binding with its receptor. Emerging evidence has shown that IGF1 is expressed at the maternal-fetal interface, but its special role in establishment and maintenance of pregnancy is largely unknown. Here, we found that the expression of IGF1 in the decidua was significantly higher than that in the endometrium. Additionally, decidua from women with normal pregnancy had high levels of IGF1 compared with that from women with unexplained recurrent spontaneous miscarriage. Estrogen and progesterone led to the increase of IGF1 in DSCs through upregulating the expression of WISP2. Recombinant IGF1 or DSCs-derived IGF1 increased the survival, reduced the apoptosis of DSCs, and downregulated the cytotoxicity of decidual NK cells (dNK) through interaction with IGF1R. These data suggest that estrogen and progesterone stimulate the growth of DSCs and impair the cytotoxicity of dNK possibly by the WISP2/IGF1 signaling pathway. [ABSTRACT FROM AUTHOR]

Immune cells and cytokines have important roles in the pathogenesis of endometriosis. However, the production and role of cytokines of T helper type 1 (Th1) and Th2 cells in the progress of endometriosis have remained to be fully elucidated. The present study reported that the interferon (IFN)-γ levels and the percentage of IFN-γ+CD4+ cells were significantly increased in the peritoneal fluid (PF) at the early stage and maintained at a higher level at the advanced stage of endometriosis; furthermore, interleukin (IL)-10 and IL-10+CD4+ cells were elevated in the advanced stage of endometriosis. In addition, IL-2 levels in the PF at the advanced stage of endometriosis were elevated and negatively associated with IFN-γ expression. In a co-culture system of ectopic endometrial stromal cells (ESCs) and macrophages, elevated IL-2 was observed, and treatment with cytokines IL-2 and transforming growth factor-β led to upregulation of the ratio of IL-2+ macrophages. IL-27-overexpressing ESCs and macrophages were able to induce a higher ratio of IL-10+CD4+ T cells. Blocking of IL-2 with anti-IL-2 neutralizing antibody led to upregulation of the ratio of IFN-γ+CD4+ T cells in the co-culture system in vitro. Recombinant human IL-10 and IFN-γ promoted the viability, invasiveness and transcription levels of matrix metalloproteinase (MMP)2, MMP9, and prostaglandin-endoperoxide synthase 2 of ESCs, particularly combined treatment with IL-10 and IFN-γ. These results suggest that IL-2 and IL-27 synergistically promote the growth and invasion of ESCs by modulating the balance of IFN-γ and IL-10 and contribute to the progress of endometriosis. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to evaluate the relationship between receipt of the substitutable-forfee vaccines (SFV) and completion of the expanded programme on immunisation (EPI). Design and settings A cross-sectional study was conducted in Fujian province, China. Participants Children who were born from 1 September 2009 to 31 August 2011, and who had been residing in the township for at least 3 months, were randomly recruited from 34 townships. Main outcomes measures Outcomes were completion rate of the EPI and coverage rate of the SFV. Results The study included 1428 children, of whom 1350 (94.5%) finished the EPI and 282 (19.7%) received at least one dose of the SFV. Administration of the SFV was associated with an increased likelihood of completing the EPI (OR=3.2, 95% CI 1.3 to 7.6 in the total sample and OR=4.0, 95% CI 1.7 to 9.6 in the subsample of children in regions with the SFV accessibility). The impact of the SFV administration on completion of the EPI was larger among children whose parents have junior school education or less (97.8% and 97.9% vs 92.5% and 91.9%, both p<0.001) and among those with a timely hepatitis B vaccine first dose (98.5% vs 94.0%, p<0.001). Conclusions Receipt of SFV is associated with increased likelihood of completion of the EPI in Fujian, China. [ABSTRACT FROM AUTHOR]

Food group intake in adolescents has many health implications. However, no study has been conducted to assess food group intake among Chinese adolescents. Objective: The purpose of this study was to evaluate food group intakes among Chinese adolescents living in Guangzhou city and the proportion of adolescents surveyed meeting the Chinese dietary guidelines, and the Chinese food pagoda for a balanced diet 2007. Methods: A school-based cross-sectional survey was conducted in Guangzhou city between October 2006 and April 2007. A random sample of 2977 adolescents, aged 12 to 17 years, was interviewed. A self-administered semi-quantitative food frequency questionnaire was used to estimate food group intakes of adolescents. Results: A high percentage of adolescents consumed too little plant foods including vegetables, fruit, and soybean products. Only 9%, 14% and 6% of adolescents surveyed reached the minimum daily recommended intake levels for vegetables, fruit, and soybean products and nuts. Nearly 70% of the studied adolescents consumed dairy less than the recommended daily intake and more than 20% adolescents reached the recommended amounts for cereals and eggs. More than one-third (35.6%) of adolescents did not meet any food group recommendations. And no adolescents reached all eight food group recommendations. An inadequate consumption of calcium and iron among adolescents was also found. Conclusions: The results of this study indicate that most adolescents living in Guangzhou city are not meeting the current recommendations for intakes of the various food groups. [ABSTRACT FROM AUTHOR]