Relaxation of the one child policy and trends in caesarean section rates and birth outcomes in China between 2012 and 2016: observational study of nearly seven million health facility births.

OBJECTIVE: To examine how the relaxation of the one child policy and policies to reduce caesarean section rates might have affected trends over time in caesarean section rates and perinatal and pregnancy related mortality in China. DESIGN: Observational study. SETTING: China's National Maternal Near Miss Surveillance System (NMNMSS). PARTICIPANTS: 6 838 582 births at 28 completed weeks or more of gestation or birth weight ≥1000 g in 438 hospitals in the NMNMSS between 2012 and 2016. MAIN OUTCOME MEASURES: Obstetric risk was defined using a modified Robson classification. The main outcome measures were changes in parity and age distributions and relative frequency of each Robson group, crude and adjusted trends over time in caesarean section rates within each risk category (using Poisson regression with a robust variance estimator), and trends in perinatal and pregnancy related mortality over time. RESULTS: Caesarean section rates declined steadily between 2012 and 2016 (crude relative risk 0.91, 95% confidence interval 0.89 to 0.93), reaching an overall hospital based rate of 41.1% in 2016. The relaxation of the one child policy was associated with an increase in the proportion of multiparous births (from 34.1% in 2012 to 46.7% in 2016), and births in women with a uterine scar nearly doubled (from 9.8% to 17.7% of all births). Taking account of these changes, the decline in caesarean sections was amplified over time (adjusted relative risk 0.82, 95% confidence interval 0.81 to 0.84). Caesarean sections declined noticeably in nulliparous women (0.75, 0.73 to 0.77) but also declined in multiparous women without a uterine scar (0.65, 0.62 to 0.77). The decrease in caesarean section rates was most pronounced in hospitals with the highest rates in 2012, consistent with the government's policy of targeting hospitals with the highest rates. Perinatal mortality declined from 10.1 to 7.2 per 1000 births over the same period (0.87, 0.83 to 0.91), and there was no change in pregnancy related mortality over time. CONCLUSIONS: China is the only country that has succeeded in reverting the rising trends in caesarean sections. China's success is remarkable given that the changes in obstetric risk associated with the relaxation of the one child policy would have led to an increase in the need for caesarean sections. China's experience suggests that change is possible when strategies are comprehensive and deal with the system level factors that underpin overuse as well as the various incentives at work during a clinical encounter

Sociodemographic and obstetric characteristics of stillbirths in China: a census of nearly 4 million health facility births between 2012 and 2014

Background Very little is known about the burden and determinants of stillbirths in China. We used data from a national surveillance system for health facility births to compute a stillbirth rate representative of all facility births in China and to explore sociodemographic and obstetric factors associated with variation in the stillbirth rate. Methods We used data from China’s National Maternal Near Miss Surveillance System between Jan 1, 2012, and Dec 31, 2014, which covers 441 hospitals in 326 urban districts and rural counties. The surveillance aimed to enumerate all maternal deaths and near misses in health facilities, and collected data prospectively for all pregnant or post-partum women admitted to the obstetric department. We restricted the analysis to births of 28 or more completed weeks of gestation or 1000 g or heavier birthweight. We examined the strength of association between sociodemographic characteristics, gestational age, and obstetric complications and stillbirths using logistic regression, taking account of the sampling strategy and clustering of births within hospitals and in cases of more than one birth per woman. Findings There were 3 956 836 births and 37 855 stillbirths, giving a stillbirth rate of 8·8 per 1000 births (95% CI 8·8–8·9). The stillbirth rate was particularly high for women younger than 15 years of age (59·9 stillbirths per 1000 births), those who had not sought antenatal care (38·3 per 1000), the unmarried (32·5 per 1000), those with no education (26·9 per 1000), or those who had had four or more births (23·2 per 1000). A high proportion (29 319 [78·2%] of 37 514) of stillbirths occurred at gestational ages of younger than 37 weeks, and about two thirds (24 787 [66·1%] of 37 514) were in women without any maternal complication at the time of birth. Of babies born at normal gestations (37–41 weeks), maternal complications substantially increased the risk of stillbirth (odds ratio comparing antepartum or intrapartum complications with no complication 3·96 [95% CI 3·66–4·29]), but only a small proportion (1638 [4·4%] of 37 514) of stillbirths fell into this group. Interpretation Our analysis of nearly 4 million births in 441 health facilities in China suggests a stillbirth rate of 8·8 per 1000 births between 2012 and 2014. Stillbirths do not feature in the Chinese Government’s 5 year plans and most information systems do not include stillbirths. The Government need to start paying attention to stillbirths and invest strategically in antenatal care, particularly for the most disadvantaged women, including the very young, unmarried, and illiterate, and those at high parity

Inonotus obliquus polysaccharide are linear molecules that alter the abundance and composition of intestinal microbiota in Sprague Dawley rats

IntroductionThe macromolecular polysaccharide Inonotus obliquus polysaccharide (IOP) is composed of various monosaccharides, and it could modulate the composition and diversity of intestinal flora. However, its impact on the intestinal flora in rats of different genders remains unclear. Therefore, this study aims to investigate the structural changes of IOP and its effects on the intestinal flora after administration in male and female rats.MethodsIn this study, the molecular weight and purity of IOP were analyzed by high-performance gel permeation chromatography (HPGPC) and phenol sulfuric acid method, and NMR was used to confirm the chemical structure of IOP. Sex hormone [testosterone (T) and estradiol (E2)] levels and intestinal microbial changes were detected by enzyme-linked immunosorbent assay (ELISA) and 16S rRNA, respectively, after gavage of IOP (100 mg/kg) in male and female Sprague Dawley (SD) rats.ResultsHPGPC analysis showed that the average molecular weight (Mw) of IOP was 4,828  Da, and the total sugar content of the purified IOP was 96.2%, indicating that the polysaccharide is of high purity. NMR revealed that IOP is a linear macromolecule with an α-D-type glucose backbone. The results of ELISA and 16S rRNA showed that the IOP increased the abundance of beneficial bacteria, such as Clostridia_UCG-014 and Prevotellaceae_NK3B31, and reduced that of harmful bacteria, such as Colidextribacter and Desulfobacterota in the intestine of both male and female rats, and IOP changed the levels of sex hormones in male and female rats. Further analyses revealed that the increase in alpha diversity was higher in male than female rats. α diversity and β diversity revealed a significant difference in the composition of cecal microbiota between male and female rats in the control group, but IOP intake reduced this difference. Meanwhile, α analysis revealed a change in the composition of bacterial flora was more stable in male than female rats.ConclusionsThis study enhances our comprehension of the IOP structure and elucidates the alterations in intestinal flora following IOP administration in rats of varying genders. Nonetheless, further investigation is warranted to explore the specific underlying reasons for these discrepancies

Characterization of a DNA Aptamer for Ovarian Cancer Clinical Tissue Recognition and in Vivo Imaging

Backgrounds/Aims: Ovarian cancer is the most lethal gynaecologic malignancy and is difficult to detect early. The inefficient early diagnosis of ovarian cancer is the main contributor to its high mortality rate. Aptamers, as chemical antibodies, are single-stranded DNA or RNA oligonucleotides that target cells or molecules with high affinity. Methods: Binding ability of R13 was measured by flow cytometry analysis. Stability of R13 was tested in blood serum of an ovarian cancer patient. Internalization of R13 was verified by confocal microscope imaging. 80 cases ovarian cancer tissues, 10 cases normal ovary tissues in a microarray and 6 fallopian tube tissues were prepared for this study. R13’s target ability was further confirmed in vivo tumor models in NOD/SCID mice. Results: In this study, we found aptamer R13 bound to ovarian cancer cells with dissociation constants in the nanomolar range. Moreover, these results were further confirmed by tissue imaging. Next we demonstrated that the targets of R13 are membrane proteins and that its internalization occurs in a caveolae-mediated and clathrin-mediated manner. The target function of R13 was determined by imaging A2780 tumours in mouse models. Conclusion: These findings suggest that R13 is a promising novel tool to diagnose and deliver drugs to treat ovarian cancer

Oxidative Stress Activates SIRT2 to Deacetylate and Stimulate Phosphoglycerate Mutase

Glycolytic enzyme phosphoglycerate mutase (PGAM) plays an important role in coordinating energy production with generation of reducing power and the biosynthesis of nucleotide precursors and amino acids. Inhibition of PGAM by small RNAi or small molecule attenuates cell proliferation and tumor growth. PGAM activity is commonly upregulated in tumor cells, but how PGAM activity is regulated in vivo remains poorly understood. Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2. Increased levels of reactive oxygen species stimulate PGAM2 deacetylation and activity by promoting its interaction with SIRT2. Substitution of endogenous PGAM2 with an acetylation mimetic mutant K100Q reduces cellular NADPH production and inhibits cell proliferation and tumor growth. These results reveal a mechanism of PGAM2 regulation and NADPH homeostasis in response to oxidative stress that impacts cell proliferation and tumor growth

NLRX1 Sequesters STING to Negatively Regulate the Interferon Response, Thereby Facilitating the Replication of HIV-1 and DNA Viruses

SummaryUnderstanding the negative regulators of antiviral immune responses will be critical for advancing immune-modulated antiviral strategies. NLRX1, an NLR protein that negatively regulates innate immunity, was previously identified in an unbiased siRNA screen as required for HIV infection. We find that NLRX1 depletion results in impaired nuclear import of HIV-1 DNA in human monocytic cells. Additionally, NLRX1 was observed to reduce type-I interferon (IFN-I) and cytokines in response to HIV-1 reverse-transcribed DNA. NLRX1 sequesters the DNA-sensing adaptor STING from interaction with TANK-binding kinase 1 (TBK1), which is a requisite for IFN-1 induction in response to DNA. NLRX1-deficient cells generate an amplified STING-dependent host response to cytosolic DNA, c-di-GMP, cGAMP, HIV-1, and DNA viruses. Accordingly, Nlrx1−/− mice infected with DNA viruses exhibit enhanced innate immunity and reduced viral load. Thus, NLRX1 is a negative regulator of the host innate immune response to HIV-1 and DNA viruses