[Retrospective analysis for 424 330 first-line screening results of non-invasive prenatal testing in Hebei province].

Objective: To evaluate the effect of noninvasive prenatal testing (NIPT) as first-line screening in fetal chromosome aneuploidy screening practice, and to provide evidence for the prevention and control strategy of birth defects. Methods: Since July 2019, Hebei province had carried out the NIPT project providing first-line screening for eligible pregnant women in the area (except for those who were not applicable). Pregnant women with high risk received genetic counseling, prenatal diagnosis and intervention guidance. Low risk and false-positive ones received continuous detection and moved to prenatal diagnosis center for counseling and diagnosis if abnormities were discovered. All pregnant women were followed up to learn about pregnancy outcomes and newborn health status. Detection results and clinical data of pregnant women participating the NIPT project from July 2019 to July 2020 were collected. The detection results and effect of NIPT were analyzed. Results: (1) Basic information of the screened population: A total of 424 330 pregnant women were screened, and 423 596 were successfully detected, with a success rate of 99.83% (423 596/424 330). The age of pregnant women was (28.8±4.5) years old; the gestational age of screening was (16.6±2.3) weeks; the proportion of advanced-age pregnant women (≥35 years old) was 10.18% (43 132/423 596); in vitro fertilization-embryo transfer (IVF-ET) rate was 1.58% (6 713/423 596); the twin rate was 1.38% (5 849/423 596); the proportion of primipara was 34.23% (144 977/423 596). (2) Screening results and detection performance: totally, 325, 73 and 20 pregnant women were diagnosed with trisomy 21, 18 and 13; the sensitivity were 99.39%, 100.00% and 100.00%; the specificity were 99.98%, 99.99% and 99.98%; the positive predictive value were 75.76%, 68.87% and 21.51%, respectively. Besides, 249 190 pregnant women were received supplementary reports as well, and 255, 10 and 9 were confirmed for sex chromosome aneuploidy, other autosomal aneuploidy and deletion/duplication syndrome; the positive predictive value were 37.78%, 6.06% and 32.14%, respectively. The sensitivity of NIPT for target trisomy (trisomy 21, 18 and 13) screening in advanced-age, IVF-ET and twin pregnant women were 99.29%, 100.00% and 90.00%, respectively; the specificity were 99.93% for all; the positive predictive value were 82.25%, 61.54% and 69.23%, respectively. Conclusions: NIPT has a significant effect and good performance in the first-line screening of fetal chromosome aneuploidy in the whole population, which might provide reference for the improvement of birth defect prevention and control strategy.

Mercury oxidation coupled to autotrophic denitrifying branched sulfur oxidation and sulfur disproportionation for simultaneous removal of Hg0 and NO.

Coupling elemental mercury (Hg0) oxidation, autotrophic denitrifying sulfur oxidation, and sulfur disproportionation offers technological potential for simultaneous Hg0 and nitric oxide (NO) removal. This study shed light on simultaneous demercuration and denitration of flue gas by a sulfur-oxidizing membrane biofilm reactor (MBfR). Removal efficiency of Hg0 and NO attained 92% and 83%, respectively in long-term operation. Taxonomic and metagenomic study revealed that a tremendous variety of Hg0-oxidizing bacteria (MOB) (Thiobacillus, Truepera, etc.), denitrifying/sulfur-oxidizing bacteria (DSOB) (Thioalkalivibrio, Thauera, etc.), sulfur-disproportionating bacteria (SDB) (Desulfobulbus, Desulfomicrobium, etc.), and multi-functional bacteria (Halothiobacillus, Thiobacillus, etc.) significantly increased in abundance during growth under feeding of Hg0 and NO in simulated flue gas. The comprehensive employment of sequential chemical extraction processes, inductive coupled mass spectrometry, X-ray diffraction, X-ray photoelectron spectroscopy, and scanning electron microscopy coupled to energy disperse spectroscopy confirmed that Hg0 was finally biologically oxidized to crystallized metacinnabar (ß-HgS) extracellular micromolecular particles. Our findings provided mechanistic insights that MOB, DSOB, and multi-functional bacteria synergistically bio-oxidized Hg0 as the initial electron donor to Hg2+ and denitrified NO as the terminal electron acceptor to N2. SDB disproportionated S0 branched from S2O32- into S2- and SO42-, and ß-HgS formation from Hg2+ and disproportionation-derived S2-, thermodynamically favored Hg0 bio-oxidation. This novel biotechnique can be a cost-effective and environmentally friendly alternative to flue gas Hg0 and NO treatment. KEY POINTS: • Combination of Hg0 bio-oxidation and autotrophic denitrifying sulfur oxidation achieved simultaneous Hg0 and NO removal. • Thiosulfate disproportionation reinforced Hg0 bio-oxidation for Hg0 removal. • Mercury-oxidizing bacteria, denitrifying/sulfur-oxidizing bacteria, and sulfur-disproportionating bacteria synergistically accomplished Hg0 and NO removal.

Bioconversion of Hg0 into HA-Hg for simultaneous removal of Hg0 and NO in a denitrifying membrane biofilm reactor.

Bacterial mercury oxidation coupled to denitrification offers great potential for simultaneous removal of elemental mercury (Hg0) and nitric oxide (NO) in a denitrifying membrane biofilm reactor (MBfR). Four potentially contributory mechanisms tested separately, namely, membrane gas separation, medium absorption, biosorption and biotransformation, which contributed 4.9%/7.2%, 8.1%/8.9%, 38.8%/9.5% and 48.2%/84.9% of overall Hg0/NO removal in MBfR. Herein, Hg0 bio-oxidation, oxidative Hg0 biosorption and denitrification played leading roles in simultaneous removal of Hg0 and NO. Living microbes performed simultaneous Hg0 bio-oxidation and denitrification, in which Hg0 as electron donor was biologically oxidized to oxidized mercury (Hg2+), while NO as the terminal electron acceptor was denitrified to N2. The Hg2+ further complexed with humic acids in extracellular polymeric substances via functional groups (-SH, -OH, -NH- and -COO-) and formed humic acids bound mercury (HA-Hg). Non-living microbial matrix performed oxidative Hg0 biosorption, in which Hg0 may be physically adsorbed by cellular matrix, then non-metabolically oxidized to Hg2+ via oxidative complexation with -SH in humic acids and finally cleavage of S-H bond and surface charge transfer led to formation of HA-Hg. Therefore, bioconversion of Hg0 to HA-Hg by Hg0 bio-oxidation and oxidative Hg0 biosorption coupled with NO denitrification to N2 dynamically cooperated to accomplish simultaneous removal of Hg0 and NO in MBfR.

[Assessment of Height Prediction Model Based on SNPs Loci].

OBJECTIVES: To establish a height prediction model of Chinese Han male based on the reported 547 height-associated single nucleotide polymorphisms （SNPs） loci in Europeans, and assess its accuracy for height estimation. METHODS: The DNA typing was analyzed in 59 Han male samples of Shandong province by Affymetrix SNP Array 6.0 chip and HiSeq 4000 sequencing platform. Prediction model was established using 547 height-associated SNPs loci as predictors and weight allele sums （WAS） as computing method. The accuracy of height prediction model was analysed using receiver operating characteristic （ROC） curve and area under curve （AUC）. RESULTS: There was no height-associated SNPs locus was found by genome-wide association studies. In present study, height prediction model was established by WAS and obtained an AUC of 0.67 （95% CI: 0.53-0.90）. CONCLUSIONS: It has reference value for predicting the height of Han male in Shandong province by WAS model based on 547 SNPs loci, while it is still necessary to further promote the accuracy of the prediction model by screening more height-associated SNPs loci with population heterogeneity.

The pharmacokinetics of orally administered fudosteine in healthy Chinese volunteers.

The pharmacokinetics of fudosteine in healthy Chinese volunteers was investigated for the first time after single- and multiple-dose administration. Five male and five female volunteers were enrolled in this study. Each subject received 400 mg fudosteine capsules (the therapeutic dose) on day 1 after overnight fasting for the single-dose study and three times daily oral administration (400 mg) for 5 consecutive days until the sixth morning for the multiple-dose study. Serial blood samples were collected at specified time intervals up to 16 hours following the first and last doses of fudosteine. Plasma harvested from the blood was separated and analyzed for fudosteine levels by a validated high-performance liquid chromatography-electrospray ionization mass spectrometry (HPLC/ESI/MS) method employing percolumn derivatization with 9-fluorenylmethyl chloroformate (FMOC-Cl). Noncompartmental analysis was used for the calculation of the total area under the plasma concentration-time curve (AUC) from time zero to time infinity and the terminal half-life (t1/2) of fudosteine. The pharmacokinetic parameters for single- and multiple-dose administration were estimated as follows: Cmax amounted to 10.13+/-4.39 microg/mL and 11.75+/-6.51 microg/mL, tmax to 0.69+/-0.36 h and 0.53+/-0.12 h and t1/2 to 2.33+/-0.63 h and 2.40+/-0.37 h, respectively. No significant differences were found between single- and multiple-dose oral administration, although gender differences were observed.

Calmodulin content in rabbit reticulocyte and the influence of opioid peptides on calmodulin activity in its membrane.

Calmodulin (CaM) content in rabbit reticulocyte and the influence of opioid peptides on CaM activity in its membrane were studied by a highly sensitive assay of CaM activity based on the stimulation of Calcium-dependent phosphodiesterase activity. The CaM contents in reticulocytes were higher than those in normal erythrocytes, both in the cytosol fraction and in the membrane fraction. Among the opioid peptides, beta-endorphin (beta-EP) and dynorphin-A-(1-13) (dyn) had a significant inhibitory effect on CaM activity in reticulocyte membrane. The effect was not antagonized by naloxone or Mr. 2266, nor influenced by increase of Ca2+ concentration, but was reversed by the addition of exogenous CaM. This implies that the action of beta-EP and dyn on reticulocyte membranes probably involves an non-opioid mechanism, in which CaM may be an important key of linkage.