Summary Background Preterm birth rates have increased significantly worldwide over the past decade. Few epidemiological studies on the incidence of preterm birth and temporal trends are available in China. This study used national monitoring data from China's National Maternal Near Miss Surveillance System (NMNMSS) to estimate the rate of preterm birth and trends between 2012 and 2018 in China and to assess risk factors associated with preterm birth. Methods In this observational study, data were sourced from the NMNMSS between Jan 1, 2012, and Dec 31, 2018. Pregnancies with at least one livebirth, with the baby born at 28 weeks of gestation or more or 1000 g or more birthweight were included. We estimated the rates of overall preterm, very preterm (born between 28 and 31 weeks’ gestation), moderate preterm (born between 32 and 33 weeks’ gestation), and late preterm (born between 34 and 36 weeks’ gestation) births in singleton and multiple pregnancies and assessed their trends over time. We used logistic regression analysis to examine the associations between preterm birth and sociodemographic characteristics and obstetric complications, considering the sampling strategy and clustering of births within hospitals. Interrupted time series analysis was used to assess the changes in preterm birth rates during the period of the universal two child policy intervention. Findings From Jan 1, 2012, to Dec 31, 2018, 9 645 646 women gave birth to at least one live baby, of whom 665 244 (6·1%) were born preterm. In all pregnancies, the overall preterm birth rate increased from 5·9% in 2012 to 6·4% in 2018 (8·8% increase; annual rate of increase [ARI] 1·3 [95% CI 0·6 to 2·1]). Late preterm births (8·8%; ARI 1·5% [0·9 to 2·2]) and very preterm births (13·3%; ARI 1·8% [0·5 to 3·0]) significantly increased from 2012 to 2018, whereas moderate preterm births did not (3·8%; ARI 0·3% [95% CI –0·9 to 1·5]). In singleton pregnancies, the overall preterm birth rate showed a small but significant 6·4% increase (ARI 1·0% [0·4 to 1·7]) over the 7 year period. In multiple pregnancies, the overall preterm birth rate significantly increased from 46·8% in 2012 to 52·7% in 2018 (12·4% increase; ARI 1·9% [1·2 to 2·6]). Compared with women who gave birth in 2012, those who gave birth in 2018 were more likely to be older (aged ≥35 years; 7·4% in 2012 vs 15·9% in 2018), have multiples (1·6% vs 1·9%), have seven or more antenatal visits (50·2% vs 70·7%), and have antepartum complications and medical disease (17·9% vs 35·1%), but they were less likely to deliver via caesarean section (47·5% vs 45·0%). Compared with the baseline period (January, 2012 to June, 2016), a higher increase in preterm birth was observed after the universal two child policy came into effect in July, 2016 (β=0·034; p=0·03). Interpretation ...

The affinity and efficacy at four subtypes (A 1 , A 2A , A 2B and A 3 ) of human adenosine receptors (ARs) of a wide range of 2-substituted adenosine derivatives were evaluated using radioligand binding assays and a cyclic AMP functional assay in intact CHO cells stably expressing these receptors. Similar to previous studies of the N 6 -position, several 2-substituents were found to be critical structural determinants for the A 3 AR activation. The following adenosine 2-ethers were moderately potent partial agonists (K i , nM): benzyl (117), 3-chlorobenzyl (72), 2-(3-chlorophenyl)ethyl (41), and 2-(2-naphthyl)ethyl (130). The following adenosine 2-ethers were A 3 AR antagonists: 2,2-diphenylethyl, 2-(2-norbornan)ethyl, R-and S-2-phenylbutyl, and 2-(2-chlorophenyl)ethyl. 2-(S-2-Phenylbutyloxy)a-denosine as an A 3 AR antagonist right-shifted the concentration-response curve for the inhibition by NECA of cyclic AMP accumulation with a K B value of 212 nM, which is similar to its binding affinity (K i = 175 nM). These 2-substituted adenosine derivatives were generally less potent at the A 1 AR in comparison to the A 3 AR, but fully efficacious, with binding K i values over 100 nM. The 2-phenylethyl moiety resulted in higher A 3 AR affinity (K i in nM) when linked to the 2-position of adenosine through an ether group (54), than when linked through an amine (310) or thioether (1960). 2-[2-(lNaphthyl)ethyloxy]adenosine (K i = 3.8 nM) was found to be the most potent and selective (>50-fold) A 2A agonist in this series. Mixed A 2A /A 3 AR agonists have been identified. Interestingly, although most of these compounds were extremely weak at the A 2B AR, 2-[2-(2-naphthyl)ethyloxy]adenosine (EC 50 = 1.4 µM) and 2-[2-(2-thienyl)-ethyloxy]adenosine (EC 50 = 1.8 (M) were found to be relatively potent A 2B agonists, although less potent than NECA (EC 50 = 140 nM).

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Hypertensive disorders in pregnancy (HDPs) are leading perinatal diseases. Using a national cohort of 2,043,182 pregnant women in China, we evaluated the association between ambient temperatures and HDP subgroups, including preeclampsia or eclampsia, gestational hypertension, and superimposed preeclampsia. Under extreme temperatures, very cold exposure during preconception (12 weeks) increases odds of preeclampsia or eclampsia and gestational hypertension. Compared to preconception, in the first half of pregnancy, the impact of temperature on preeclampsia or eclampsia and gestational hypertension is opposite. Cold exposure decreases the odds, whereas hot exposure increases the odds. Under average temperatures, a temperature increase during preconception decreases the risk of preeclampsia or eclampsia and gestational hypertension. However, in the first half of pregnancy, temperature is positively associated with a higher risk. No significant association is observed between temperature and superimposed preeclampsia. Here we report a close relationship exists between ambient temperature and preeclampsia or eclampsia and gestational hypertension.

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Different mechanisms have been proposed to explain the permeation of charged compounds through lipid membranes. Overall, it is expected that an ion-induced defect permeation mechanism, where substantial membrane deformations accompany ion movement, should be dominant in thin membranes but that a solubility–diffusion mechanism, where ions partition into the membrane core with large associated dehydration energy costs, becomes dominant in thicker membranes. However, while this physical picture is intuitively reasonable, capturing the interconversion between these two permeation mechanisms in molecular dynamics (MD) simulations based on atomic models is challenging. In particular, simulations relying on nonpolarizable force fields are artificially unfavorable to the solubility–diffusion mechanism, as induced polarization of the nonpolar hydrocarbon is ignored, causing overestimated free energy costs for charged molecules to enter into this region of the membrane. In this study, all-atom MD simulations based on nonpolarizable and polarizable force fields are used to quantitatively characterize the permeation process for the arginine side chain analog methyl-guanidinium through bilayer membranes of mono-unsaturated phosphatidylcholine lipids with and without cholesterol, resulting in thicknesses spanning from ∼24 to ∼42 Å. With simulations based on a nonpolarizable force field, ion translocation can take place solely through an ion-induced defect mechanism, with free energy barriers increasing linearly from 14 to 40 kcal/mol, depending on the thickness. However, with simulations based on a polarizable force field, ion translocation is predominantly dominated by an ion-induced defect mechanism in thin membranes, which progressively converts to a solubility–diffusion mechanism as the membranes get thicker. The transition between the two mechanisms occurs at a thickness of ∼29 Å, with lipid tails of 22 or more carbon atoms. This situation appears to represent the upper limit for ion-induced defect permeation within the current polarizable models. Beyond this thickness, it becomes energetically preferable for the ion to dehydrate and partition into the membrane corea phenomenon that cannot be captured using the nonpolarizable models. Induced electronic polarizability therefore leads not just to a shift in permeation energetics but to an interconversion between two strikingly different physical mechanisms. The result highlights the importance of induced polarizability in modeling lipid membranes.

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