Aurora-A inhibitor synergistically enhances the inhibitory effect of anlotinib on hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly malignant tumor with a global prevalence. In addition to the existing clinical guidelines, the effectiveness of anlotinib and Aurora-A inhibitors in treating HCC has also been demonstrated. However, Anlotinib, as an anti-angiogenesis therapy, has shown significant benefits in clinical trials but is limited by its single-agent treatment and the development of drug resistance. Aurora-A inhibitors are currently being tested in clinical trials but have limited efficacy. Combination therapy may offer clear advantages over monotherapy in this context. METHODS: In this study, we used HCC cell lines to investigate whether the combination of the two drugs could enhance their individual strengths and mitigate their weaknesses, thereby providing greater clinical benefits both in vitro and in vivo. RESULTS: Our findings confirmed that the Aurora-A inhibitor alisertib and anlotinib exhibited a time-dose-dependent inhibitory effect on HCC cells. In vitro cytological experiments demonstrated that the combination of the two drugs synergistically inhibited cell proliferation, invasion, and metastasis, while promoting cell apoptosis. Furthermore, we identified the underlying molecular mechanism by which the combination of the Aurora-A inhibitor alisertib and anlotinib inhibited HCC through the inhibition of the NF-ĸB signaling pathway. CONCLUSIONS: In summary, we have demonstrated the effectiveness of combining anlotinib with an Aurora-A inhibitor, which expands the potential applications of anlotinib in the clinical treatment of HCC in the future.

Effects of Timing and Types of Protein Supplementation on Improving Muscle Mass, Strength, and Physical Performance in Adults Undergoing Resistance Training: A Network Meta-Analysis.

Precise protein supplementation strategies for muscle improvement are still lacking. The timing or type of protein supplementation has been debated as a window of opportunity to improve muscle mass, strength, and physical performance. We conducted a network meta-analysis of randomized controlled trials with protein supplements and resistance training. PubMed, Web of Science, Cochrane Library, and SPORTDiscus databases were searched until May 1, 2023. We included 116 eligible trials with 4,711 participants that reported on 11 timing and 14 types of protein supplementation. Compared with placebo, protein supplementation after exercise (mean difference [MD]: 0.54 kg [95% confidence intervals 0.10, 0.99] for fat-free mass, MD: 0.34 kg [95% confidence intervals 0.10, 0.58] for skeletal muscle mass) and at night (MD: 2.85 kg [0.49, 5.22] for handgrip strength, MD: 12.12 kg [3.26, 20.99] for leg press strength) was most effective in improving muscle mass and strength, respectively (moderate certainty). Milk proteins (milk, whey protein, yogurt, casein, and bovine colostrum), red meat, and mixed protein were effective for gains in both muscle mass and strength (moderate certainty). No timing or type of protein showed a significant enhancement in physical performance (timed up-to-go test, 6-min walk test, and gait speed). Pre/postexercise and Night are key recommended times of protein intake to increase muscle mass and strength, respectively. Milk proteins are the preferred types of protein supplements for improving muscle mass and strength. Future randomized controlled trials that directly compare the effects of protein timing or types are needed. This trial was registered at International Prospective Register of Systematic Reviews as CRD42022358766.

Adverse associations between maternal deoxynivalenol exposure and birth outcomes: a prospective cohort study in China.

BACKGROUND: Deoxynivalenol (DON), one of the most prevalent mycotoxins, has been found to cause fetal growth retardation in animals. However, limited evidence exists regarding its effects on pregnant women. METHODS: Maternal urinary concentration of total DON (tDON) and free DON (fDON) in the second trimester was measured using liquid chromatography with tandem mass spectrometry. Provisional daily intake (PDI) of DON was calculated based on tDON concentration. Linear and logistic regression models were used to evaluate the association between DON exposure levels and birth weight, birth length, and the risk of small for gestational age (SGA). RESULTS: Among 1538 subjects, the median concentrations of tDON and fDON were 12.1 ng/mL and 5.1 ng/mL, respectively. The PDI values revealed that the median DON intake was 0.7 µg/kg bw, and 35.9% of the total population exceeded the provisional maximum tolerable daily intake (PMTDI) of 1 µg/kg bw. Compared with the lowest tertile, birth weight decreased by 81.11 g (95% CI: -127.00, -35.23) for tDON (P-trend < 0.001) and 63.02 g (95% CI: -108.72, -17.32) for fDON (P-trend = 0.004) in the highest tertile. Each unit increase in Ln-tDON and Ln-fDON was also inversely associated with birth weight. Furthermore, compared to those who did not exceed PMTDI, pregnant women whose PDI exceeded PMTDI had lower birth weight (ß = -79.79 g; 95% CI: -119.09, -40.49) and birth length (ß = -0.21 cm; 95% CI: -0.34, -0.07), and a higher risk of SGA (OR = 1.48; 95% CI: 1.02, 2.15) in their offspring. Similar associations with birth weight, birth length, and SGA were found when comparing the highest tertile of PDI to the lowest tertile (all P-trend < 0.05). CONCLUSIONS: Maternal DON exposure is related to decreased birth weight. Our findings implicate that DON exposure during pregnancy may cause fetal growth faltering, and measures should be taken to reduce DON exposure in pregnant women.

Dephasing of ultracold cesium 80D5/2-Rydberg electromagnetically induced transparency.

We study Rydberg electromagnetically induced transparency (EIT) of a cascade three-level atom involving 80D5/2 state in a strong interaction regime employing a cesium ultracold cloud. In our experiment, a strong coupling laser couples 6P3/2 to 80D5/2 transition, while a weak probe, driving 6S1/2 to 6P3/2 transition, probes the coupling induced EIT signal. At the two-photon resonance, we observe that the EIT transmission decreases slowly with time, which is a signature of interaction induced metastability. The dephasing rate γOD is extracted with optical depth OD = γODt. We find that the optical depth linearly increases with time at onset for a fixed probe incident photon number Rin before saturation. The dephasing rate shows a nonlinear dependence on Rin. The dephasing mechanism is mainly attributed to the strong dipole-dipole interactions, which leads to state transfer from nD5/2 to other Rydberg states. We demonstrate that the typical transfer time τ0(80D) obtained by the state selective field ionization technique is comparable with the decay time of EIT transmission τ0(EIT). The presented experiment provides a useful tool for investigating the strong nonlinear optical effects and metastable state in Rydberg many-body systems.

Mycorrhizae enhance reactive minerals but reduce mineral-associated carbon.

Soil organic carbon (C) is the largest active C pool of Earth's surface and is thus vital in sustaining terrestrial productivity and climate stability. Arbuscular mycorrhizal fungi (AMF) form symbioses with most terrestrial plants and critically modulate soil C dynamics. Yet, it remains unclear whether and how AMF-root associations (i.e., mycorrhizae) interact with soil minerals to affect soil C cycling. Here we showed that the presence of both roots and AMF increased soil dissolved organic C and reactive Fe minerals, as well as litter decomposition and soil CO2 emissions. However, it reduced mineral-associated C. Also, high-resolution nanoscale secondary ion mass spectrometry images showed the existence of a thin coating (0.5-1.0 µm thick) of 56 Fe16 O- (Fe minerals) on the surface of 12 C14 N- (fungal biomass), illustrating the close physical association between fungal hyphae and soil Fe minerals. In addition, AMF genera were divergently related to reactive Fe minerals, with Glomus being positively but Paraglomus and Acaulospora negatively correlated with reactive Fe minerals. Moreover, the presence of roots and AMF, particularly when combined with litter addition, enhanced the abundances of several critical soil bacterial genera that are associated with the formation of reactive minerals in soils. A conceptual framework was further proposed to illustrate how AMF-root associations impact soil C cycling in the rhizosphere. Briefly, root exudates and the inoculated AMF not only stimulated the decomposition of litter and SOC and promoted the production of CO2 emission, but also drove soil C persistence by unlocking mineral elements and promoting the formation of reactive minerals. Together, these findings provide new insights into the mechanisms that underlie the formation of reactive minerals and have significant implications for understanding and managing soil C persistence.

Association of elevated mid-pregnancy maternal plasma ferritin concentrations and triglyceride concentrations with the risk of gestational diabetes mellitus: A prospective cohort study.

OBJECTIVE: Ferritin levels are well known to be associated with gestational diabetes mellitus (GDM). However, the association of the combination of ferritin and triglyceride (TG) levels in early mid-pregnancy with GDM has not been studied in depth. We investigated the independent and combined relationships of plasma ferritin and TG concentrations with the risk of GDM as well as the mediation effect of TG on ferritin. METHODS: We analysed 2071 pregnant women from the Tongji Maternal and Child Health Cohort who had their plasma ferritin and TG concentrations measured at 11-20 weeks of gestation. Associations between ferritin and TG concentrations and GDM risk were estimated using multivariable logistic regression models. Youden's index was calculated to find the cut-off values of ferritin and TG by ROC curve analysis. The mediation effect of the TG concentration on the ferritin level with GDM risk was explored by a mediation analysis. RESULTS: A total of 264 (12.3%) participants developed GDM. The median and IQR of ferritin was 53.9 (30.5-92.7) ng/mL. After adjusting for potential confounders, the relative risks (RRs) and 95% confidence intervals of GDM were 2.19 (1.42, 3.39) for ferritin and 2.02 (1.37, 2.97) for TG. The adjusted RR for combination was 2.40 (1.62, 3.55). Moreover, we found that the TG concentration mediated 15.0% of the total effect of the ferritin concentration on the risk of GDM. CONCLUSIONS: Women with a combination of both high plasma ferritin (˃55.7 ng/mL) and high TG (˃1.9 mmoL/L) were at the highest risk of GDM. Additionally, we have revealed for the first time that an elevated maternal TG concentration in early pregnancy mediates the relationship between ferritin concentration and GDM risk. TRIAL REGISTRATION: This trial is registered at https://ClinicalTrials.gov as NCT03099837.

Association of Breastfeeding Practices During the First 3 Months with Infant Sleep Trajectories: A Prospective Cohort Study.

BACKGROUND: Breastfeeding has numerous effects on maternal and child health. The effect of breastfeeding on infant sleep remains inconclusive. OBJECTIVES: We aimed to examine whether full breastfeeding (FBF) during the first 3 mo is associated with longitudinal infant sleep trajectories in their first 2 y of life. METHODS: The study was embedded in the Tongji Maternal and Child Health Cohort study. Information on infant feeding practices was collected at 3 mo of age, and maternal/child pairs were assigned to the FBF or the non-FBF group (including partially breastfeeding and exclusive formula feeding) on the basis of feeding practices during the first 3 mo of life. Sleep data of infants were obtained at 3, 6, 12, and 24 mo. Total, night, and day sleep trajectories across 3 to 24 mo were estimated with group-based models. Each sleep trajectory was differentiated on the basis of sleep duration at 3 mo (long/moderate/short) and the interval from 6 to 24 mo (moderate/short). Multinomial logistic regression was used to investigate the association of breastfeeding practices with infant sleep trajectories. RESULTS: Among the 4056 infants studied, 2558 (63.1%) received FBF for 3 mo. When compared with FBF infants, non-FBF infants had shorter sleep duration at 3, 6, and 12 mo (P < 0.01). Non-FBF infants were more likely to experience Moderate-Short (OR: 1.31; 95% CI: 1.06, 1.61) and Short-Short (OR: 1.56; 95% CI: 1.12, 2.16) total sleep trajectories and more likely to experience Moderate-Short (OR: 1.84; 95% CI: 1.22, 2.77), and Short-Moderate (OR: 1.40; 95% CI: 1.06, 1.85) night sleep trajectories than FBF infants. CONCLUSIONS: Full breastfeeding for ≥3 mo were positively associated with longer infant sleep duration. Infants fully breastfed were more likely to experience better sleep trajectories characterized by longer duration in their first 2 y of life. Full breastfeeding may benefit infants through healthy sleep.

Vitamin D supplementation and lower respiratory tract infection in infants: a nested case-control study.

PURPOSE: To assess the association between vitamin D (VD) supplementation and the risk of lower respiratory tract infection (LRTI) among infants. METHODS: This is a nested case-control study from an ongoing prospective birth cohort in Wuhan from 2013. Cases were subjects free of neonatal pneumonia but later developed LRTI during infancy, who were matched with five randomly selected controls by infant sex, birth year, and birth season. We included 190 cases and 950 controls in the final analysis. The primary outcome was the first LRTI incident and the exposure was VD supplementation from birth to the index endpoint. The association between VD supplementation and LRTI risk was assessed using the Cox proportional-hazards regression model. RESULTS: Infants taking supplements had a 59% relative reduction in the hazard ratio of LRTI (HR = 0.41; 95% CI 0.26, 0.64) compared to those not supplemented. There was a linear relationship between LRTI risk and VD supplementation within range of 0-603 IU/day: for each 100 IU per day increment in VD supplementation, infants experienced a 21% lower risk of developing LRTI (adjusted HR: 0.79; 95% CI 0.71, 0.89). The linear relationship was stably observed in the sensitivity analyses as well. CONCLUSIONS: VD supplementation was associated with the reduced risk of LRTI throughout infancy, and the optimal supplementation dose for infants may be beyond the current recommendation.

Patterns of maternal gestational weight gain in association with allergic diseases in offspring: A prospective cohort study.

OBJECTIVE: To evaluate the association between patterns of gestational weight gain (GWG) and allergic diseases in offspring. DESIGN: Prospective cohort study. SETTING: Prenatal clinics in Wuhan, China. POPULATION: A cohort of 2546 mother and offspring pairs were enrolled before 16 weeks of gestation and followed up to 24 months postpartum. METHODS: Maternal body weights were measured regularly during pregnancy, and their GWG patterns were estimated using the growth mixture model. Robust Poisson models were used to evaluate relative risk (RR) and 95% CI after multivariable adjustment. MAIN OUTCOME MEASURES: Offspring atopic allergy and allergic contact dermatitis were defined according to a physician's diagnosis reported by the mother, and food allergy was reported by the mother. RESULTS: Three GWG patterns were identified: 18.1% (461) of the women were described as pattern 1, characterised by rapid GWG earlier in pregnancy; 56.6% (1442) of the women were described as pattern 2, with steady GWG throughout pregnancy; and 25.3% (643) of the women was described as pattern 3, with rapid GWG later in pregnancy. By the age of 24 months, 360 (14.1%), 109 (4.3%) and 757 (29.7%) offspring had atopic allergy, allergic contact dermatitis or food allergy, respectively. Compared with women in GWG pattern 2, the RRs (95% CIs) among women in pattern 1 were 0.74 (0.55-0.99) for atopic allergy, 0.64 (0.36-1.15) for allergic contact dermatitis and 0.95 (0.81-1.12) for food allergy. CONCLUSIONS: Maternal GWG pattern characterised by rapid GWG earlier in pregnancy was associated with a lower risk of atopic allergy in offspring.

Metabolism and elimination kinetics of mono-hydroxylated PAHs metabolites following single exposure to different combinations of PAH4 in rats.

The metabolism of polycyclic aromatic hydrocarbons (PAHs) and the elimination kinetics of their mono-hydroxylated metabolites (OH-PAHs) following single exposure to different combinations of four PAHs (PAH4) were studied. Male Sprague-Dawley rats were orally exposed to a single dose of benzo[a]pyrene (B[a]P) or PAH2 (B[a]P + chrysene), PAH3 (B[a]P + chrysene + benz[a]anthracene), and PAH4 (B[a]P + chrysene + B[a]A + benzo[b]fluoranthene) with each combination adjusted to the same dose of individual compound. OH-PAHs including 3-hydroxybenzo[a]pyrene, 3-hydroxychrysene, 3-hydroxybenz[a]anthracene, and 1-hydroxypyrene (1-OHP) were detected in serum and urine samples collected at six intervals over a 72-h period post-dosing. The hepatic mRNA levels of cytochrome P450 (CYPs) were determined to ascertain the expression induction of PAHs metabolic enzymes. Results showed OH-PAHs (except 1-OHP) peaked within 8 h in serum and were excreted from urine within 24-48 h. The serum and urinary concentration of 3-hydroxybenzo[a]pyrene was significantly increased after PAH4 exposure compared with other PAHs combinations. Inversely, urinary concentration of 3-hydroxychrysene was decreased after PAH4 exposure, and the kinetics of 3-hydroxybenz[a]anthracene or 1-OHP were not different depending on the PAHs combinations. Also, CYPs were markedly induced by PAHs. Notably, the induction levels of CYP1A1 and CYP1B1 were significantly higher after PAH4 exposure compared with B[a]P exposure. The results indicated the metabolism of B[a]P was accelerated after PAH4 exposure which might be partly due to the induction of CYPs. These results confirmed PAHs are rapidly metabolized and suggested potential interactions of PAHs may happen among PAH4 mixture.

Association of maternal dietary patterns derived by multiple approaches with gestational diabetes mellitus: a prospective cohort study.

We used two a priori diet scores [Mediterranean diet (aMed) and Diet Balance Index (DBI)] and two a posteriori approaches [principal components analysis (PCA) and reduced-rank regression (RRR)] to examine the association of maternal dietary patterns with risk of gestational diabetes mellitus (GDM) and blood glucose among 2202 pregnant women in the Tongji Birth Cohort. Compared to the highest quartile of the aMed and legumes-vegetables-fruits (derived by PCA) scores, the fasting blood glucose (FBG) levels were higher in the lower quartiles (p-trend < 0.05). Lower scores of the meats-eggs-dairy (derived by PCA) and eggs-fish patterns (derived by RRR; characterised by higher intakes of freshwater fish, eggs, and lower intakes of leafy and cruciferous vegetables and fruits) were associated with decreased FBG levels (p-trend < 0.05). Similarities were found across approaches that some dietary patterns were associated with FBG, but not with postprandial glucose and GDM risk.

Increased food diversity in the first year of life is inversely associated with allergic outcomes in the second year.

BACKGROUND: The evidence on the relationship between diet diversity in early life and allergic outcomes was few and inconsistent. We sought to determine the association of food diversity in the first year of life with allergic outcomes in the second year. METHODS: Two thousand two hundred fifty-one mother-infant pairs from Tongji Maternal and Child Health Cohort (TMCHC) were involved in the study. Information on complementary foods introduction was obtained by telephone interview at 6- and 12-month postpartum follow-up. Any doctor-diagnosed allergic diseases in the second year were recorded at 2-year postpartum follow-up. Food allergies in infancy were assessed and self-reported by mothers at each postpartum follow-up. Multivariable logistic regression was used to examine the effect of food diversity at 6 and 12 months of age on later allergic diseases and food allergy. RESULTS: A total of 135 (6.0%) infants reported allergic diseases at between 1 and 2 years of age. Independent of food allergy history of infants and other potential confounders, less food diversity at 6 months of age was associated with increased risk of later allergic diseases (OR 2.17, 95% CI 1.04-4.50 for 0 vs. 3-6 food groups). By 12 months of age, significant inverse associations with later allergic diseases (OR 2.35, 95% CI 1.03-5.32 for 1-5 vs. 8-11 food groups, and OR 1.98, 95% CI 1.16-3.37 for 6-7 vs. 8-11 food groups) and food allergy (OR 2.10, 95% CI 1.29-3.42 for 1-5 vs. 8-11 food groups) were observed. Children with higher food diversity in both periods had the lowest risk of allergic diseases during the second year of life. CONCLUSIONS: A more diverse diet within the first year of life was associated with reduced risk of allergic diseases at 1-2 years of age. Introducing higher diversity of foods from 6 to 12 months of age might be an effective strategy to improve the allergy outcomes of infants in later life.

Association of maternal low-carbohydrate-diet score during pregnancy with allergic diseases at 2 years of age.

BACKGROUND: We prospectively evaluated the association between low-carbohydrate-diet (LCD) score during pregnancy and the risk of allergic diseases in infants up to 2 years. METHODS: Participants were from a prospective mother-offspring cohort study in Wuhan, China. LCD score was calculated according to the percentage of dietary energy intake from carbohydrate, protein, and fat assessed in late pregnancy using validated food frequency questionnaires. Allergic diseases, including immunoglobulin E (IgE)-mediated allergic diseases, allergic contact dermatitis, and food allergy, were recorded at 3, 6, 12, and 24 months postpartum follow-up. Poisson regression models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Among 1636 mother-infant pairs included in the present analysis, 230 infants (14.1%) with IgE-mediated allergic diseases, 77 (4.7%) with allergic contact dermatitis, and 488 (29.8%) with food allergy were, respectively, reported. Independent of total energy intake and other potential confounders, both the lowest quintile (RR, 1.77; 95% CI, 1.13-2.77) and the highest quintile (RR, 1.72; 95% CI, 1.22-2.63), were associated with the risk of IgE-mediated allergic diseases compared with the middle quintile. Among high-carbohydrate-diet pregnant women, substituting 5% of energy from either protein or fat for carbohydrate was associated with a lower risk of IgE-mediated allergic diseases. While among low-carbohydrate-diet pregnant women, substituting 5% of energy from carbohydrate, especially high-quality carbohydrate, for fat was associated with a lower risk of IgE-mediated allergic diseases. CONCLUSION: Maternal low carbohydrate-high protein and fat, and high carbohydrate-low protein and fat diet were both associated with an increased risk of allergic diseases in the infants up to 2 years. This study may provide an intervention strategy for allergy prevention in early childhood.

Timing of gestational weight gain in association with birth weight outcomes: a prospective cohort study.

Maternal gestational weight gain (GWG) is an important determinant of infant birth weight, and having adequate total GWG has been widely recommended. However, the association of timing of GWG with birth weight remains controversial. We aimed to evaluate this association, especially among women with adequate total GWG. In a prospective cohort study, pregnant women's weight was routinely measured during pregnancy, and their GWG was calculated for the ten intervals: the first 13, 14-18, 19-23, 24-28, 29-30, 31-32, 33-34, 35-36, 37-38 and 39-40 weeks. Birth weight was measured, and small-for-gestational-age (SGA) and large-for-gestational-age were assessed. Generalized linear and Poisson models were used to evaluate the associations of GWG with birth weight and its outcomes after multivariate adjustment, respectively. Of the 5049 women, increased GWG in the first 30 weeks was associated with increased birth weight for male infants, and increased GWG in the first 28 weeks was associated with increased birth weight for females. Among 1713 women with adequate total GWG, increased GWG percent between 14 and 23 weeks was associated with increased birth weight. Moreover, inadequate GWG between 14 and 23 weeks, compared with the adequate GWG, was associated with an increased risk of SGA (43 (13·7 %) v. 42 (7·2 %); relative risk 1·83, 95 % CI 1·21, 2·76). Timing of GWG may influence infant birth weight differentially, and women with inadequate GWG between 14 and 23 weeks may be at higher risk of delivering SGA infants, despite having adequate total GWG.

Plasma Manganese Levels and Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study.

Manganese (Mn) intake has been found to be linked with risk of type 2 diabetes. However, the role of Mn in the development of gestational diabetes mellitus (GDM) remains to be investigated. This prospective study included pregnant women from the Tongji Maternal and Child Health Cohort. A total of 2327 participants with plasma specimens before 20 weeks were included. Among the pregnant women, 9.7% (225/2327) were diagnosed with GDM. After adjustment, pregnant women with the third and highest quartile of plasma Mn levels had 1.31-fold (RR, 2.31 [1.48, 3.61]) and 2.35-fold (RR, 3.35 [2.17, 5.17]) increased risk of GDM compared with those with the lowest quartile. A 1 standard deviation increment of ln-transformed plasma Mn levels (0.53 µg/L) was related to elevated risks of GDM with RRs of 1.28 [1.17, 1.40]. The positive associations between Mn and GDM remained consistent in all the subgroups. The weighted quantile sum index was significantly related to GDM (RR, 1.60 [1.37, 1.86]). The contribution of Mn (58.69%) to the metal mixture index was the highest related to GDM. Higher plasma Mn levels were found to be linked with elevated fasting and 2 h post-load blood glucose. This study revealed relationships of higher plasma Mn levels in early pregnancy and increased risk of GDM, suggesting that though essential, excess Mn in the body might be a potential important risk factor for GDM.

Effect of maternal vitamin D status on risk of adverse birth outcomes: a systematic review and dose-response meta-analysis of observational studies.

PURPOSE: Accumulating evidence suggests that vitamin D deficiency increases the risk of adverse perinatal outcomes. However, the dose-response relationship between maternal vitamin D status and adverse birth outcomes remains unclear. Focusing on prospective observational studies, we aimed to explore the dose-response relationship of vitamin D status with the risk of low birth weight (LBW), macrosomia (MA), preterm birth (PTB), small for gestational age (SGA), and intrauterine growth restriction (IUGR). METHODS: Databases including PubMed, Embase, Scopus, and Web of Science were used up to 19 January 2021 to search for observational studies that fulfilled criteria as follows: cohort studies, case-cohort studies, or nested case-control studies. Random-effects models were used to pool relative risks (RRs) and 95% confidence intervals (CIs) in the observational studies. RESULTS: A total of 72 publications were included in this systematic review and 71 in the meta-analysis. Maternal 25-hydroxyvitamin D (25(OH)D) concentrations were inversely associated with the risk of LBW (RR: 0.65; 95% CI 0.48-0.86), PTB (RR: 0.67; 95% CI 0.57-0.79), and SGA (RR: 0.61; 95% CI 0.49-0.76) in the highest versus lowest meta-analysis, but not associated with MA and IUGR. Linear dose-response analysis showed that each 25 nmol/L increase in 25(OH)D was associated with a 6% and 10% reduction in the risk of PTB (RR: 0.94; 95% CI 0.90-0.98) and SGA (RR: 0.90; 95% CI 0.84-0.97), respectively. CONCLUSION: Our study suggests that a sufficient vitamin D status during pregnancy is protective against the risk of LBW, PTB, and SGA.

The association of maternal vaginal bleeding and progesterone supplementation in early pregnancy with offspring outcomes: a prospective cohort study.

BACKGROUND: Progesterone is widely used to improve the adverse pregnancy outcomes related to vaginal bleeding during early pregnancy. However, the evidence of its effectiveness is equivocal. METHODS: Six thousand six hundred fifteen mother-infant pairs from Tongji Maternal and Child Health Cohort (TMCHC) were involved in the study. Information on vaginal bleeding, progesterone administration in early pregnancy were obtained at enrolment. Birth outcomes were obtained from the hospital notes. Body weight of the infants at 12 months of age was collected by telephone interview. Multivariable logistic regression was conducted to estimate the effect of vaginal bleeding and progesterone administration in early pregnancy on birth outcomes and weight status of infants at 12 months of age. RESULTS: 21.4% (1418/6615) participants experienced bleeding in early pregnancy, and 47.5% (674/1418) of them were treated with progesterone. There were no significant associations between progesterone supplementation in early pregnancy and offspring outcomes. Compared to women without bleeding or any therapy, women with bleeding and progesterone therapy experienced increased risk of preterm (OR 1.74, 95% CI 1.21-2.52), and delivering a small-for-gestational-age (SGA) (OR 1.46, 95% CI 1.07-1.98) or low birth weight (LBW) (OR 2.10, 95% CI 1.25-3.51) neonate, and offspring of them had an increased risk of weight for age z-score (WAZ) < -1 at 12 months of age (OR 1.79, 95%CI 1.01-3.19). CONCLUSIONS: Offspring of mothers with bleeding and progesterone therapy were more likely to be a premature, SGA or LBW neonate, and had lower weight at 12 months of age. Progesterone supplementation may have no beneficial effect on improving adverse offspring outcomes related to early vaginal bleeding. TRIAL REGISTRATION: TMCHC was registered at clinicaltrials.gov as NCT03099837 on 4 April 2017.

Association of maternal neutrophil count in early pregnancy with the development of gestational diabetes mellitus: a prospective cohort study in China.

OBJECTIVE: We evaluated the potential role of maternal serum levels of neutrophils in the first trimester of pregnancy in the prediction of gestational diabetes mellitus (GDM). METHODS: This prospective cohort study enrolled singleton pregnant women before gestational weeks 16 and evaluated them until delivery. Among the 1467 pregnant women who performed prenatal care before 14 weeks of gestation in the cohort, a total of 731 were eligible for the final analysis. The associations between neutrophil counts, white blood cell count, neutrophil to lymphocyte ratio, and GDM (assessed by a 75-g oral glucose tolerance test between 24 and 28 weeks) were evaluated by multivariate logistic regression. RESULTS: Neutrophil count outperformed the neutrophil to lymphocyte ratio and white blood cell count in predicting GDM occurrence. We applied a smoothing function and found that neutrophil count was associated with both fasting blood glucose (FBG) (p=.0149) and 1-h postprandial blood glucose (PBG) (p=.0187) after adjustment pre-pregnancy body mass index, family history of diabetes, and age. Logistic regression analysis found that the highest neutrophil count level (6.28-14.73 × 109/L) had a 1.85-fold (95% CI 1.10, 3.09) increased risk of GDM compared with that of the lowest tertile (1.47-4.82 × 109/L). CONCLUSIONS: The results indicated an association between higher neutrophil levels and GDM occurrence.

Distinction of electromagnetically induced transparency and Autler-Towners splitting in a Rydberg-involved ladder-type cold atom system.

Electromagnetically induced transparency (EIT) and Autler-Townes splitting (ATS) are two similar quantum coherent phenomena but have different mechanisms and applications. Akaike information criteria (AIC), an objective method to discriminate EIT and ATS from an experimental viewpoint, has been employed in a variety of systems. Here we use AIC method to quantitively discriminate a series of spectra of cold atoms in a Rydberg-involved upper-driving ladder-type. The derived weights of EIT and ATS reflect that our spectra change from EIT-ATS intermediate region to ATS-dominated region along Rabi frequency of coupling field increases. We find that there are two factors affecting EIT-ATS weights in a Rydberg-involved three-level system: dephasing rate, induced by the interactions among Rydberg atoms, makes the EIT-ATS crossover move to the direction of low Rabi frequency of coupling field and the experimental noise makes the difference between EIT and ATS weights reduce at elsewhere. Our investigation could provide a meaningful reference for the observations and applications of Rydberg-involved quantum coherent spectroscopy.

The effect of maternal seafood consumption on perinatal outcomes: a systematic review and dose-response meta-analysis.

Observational studies have suggested inconsistent results between maternal seafood consumption and the risk of adverse birth outcomes. We aimed to explore the possible dose-response relationship between seafood consumption during pregnancy and perinatal outcomes. A systematic search was performed with the use of PubMed, Web of Science, Embase and Cochrane Library from inception to October 27, 2019. Random-effects model was used to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Dose-response meta-analysis was carried out by using generalized least-squares regression and restricted cubic splines. Twenty-one studies with a total of 571641 participants were included in the analyses. A 45 g/day increment in seafood consumption was associated with a reduced risk of low birth weight (LBW) (OR: 0.65, 95% CI: 0.47 to 0.90) and small for gestational age (SGA) (OR: 0.84, 95% CI: 0.71 to 0.98). Additionally, there was a non-linear dose-response relationship between maternal seafood consumption and the risk of preterm birth (PTB), with no further benefit observed when intake above 45 g/day. The results for subtypes of seafood showed a modest J-shaped association between fatty fish and PTB, and the lowest risk was observed with the consumption of 30 g/day. In conclusion, higher total seafood consumption during pregnancy was associated with a lower risk of adverse birth outcomes, but the consumption of fatty fish should not exceed 30 grams per day. These findings could provide substantial evidence for dietary recommendations regarding seafood intake for pregnant women. This review was registered in PROSPERO (CRD42020152912).