Inverse association between maternal serum concentrations of trace elements and risk of spontaneous preterm birth: a nested case-control study in China.

Few studies have evaluated the joint effect of trace elements on spontaneous preterm birth (SPTB). This study aimed to examine the relationships between the individual or mixed maternal serum concentrations of Fe, Cu, Zn, Se, Sr and Mo during pregnancy, and risk of SPTB. Inductively coupled plasma MS was employed to determine maternal serum concentrations of the six trace elements in 192 cases with SPTB and 282 controls with full-term delivery. Multivariate logistic regression, weighted quantile sum regression (WQSR) and Bayesian kernel machine regression (BKMR) were used to evaluate the individual and joint effects of trace elements on SPTB. The median concentrations of Sr and Mo were significantly higher in controls than in SPTB group (P < 0·05). In multivariate logistic regression analysis, compared with the lowest quartile levels of individual trace elements, the third- and fourth-quartile Sr or Mo concentrations were significantly associated with reduced risk of SPTB with adjusted OR (aOR) of 0·432 (95 CI < 0·05). In multivariate logistic regression analysis, compared with the lowest quartile levels of individual trace elements, the third- and fourth-quartile Sr or Mo concentrations were significantly associated with reduced risk of SPTB with adjusted aOR of 0·432 (95 % CI 0·247, 0·756), 0·386 (95 % CI 0·213, 0·701), 0·512 (95 % CI 0·297, 0·883) and 0·559 (95 % CI 0·321, 0·972), respectively. WQSR revealed the inverse combined effect of the trace elements mixture on SPTB (aOR = 0·368, 95 % CI 0·228, 0·593). BKMR analysis confirmed the overall mixture of the trace elements was inversely associated with the risk of SPTB, and the independent effect of Sr and Mo was significant. Our findings suggest that the risk of SPTB decreased with concentrations of the six trace elements, with Sr and Mo being the major contributors.

[Clinical analysis of monochorionic-diamniotic twins with genetic discordance].

OBJECTIVE: To explore the genetic etiology of 5 cases of monochorionic-diamniotic (MCDA) with genetic discordance. METHODS: 148 cases of MCDA twins who were diagnosed by amniocentesis at the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region from January 2016 to June 2020 were selected as the study subjects. Relevant clinical data of the pregnant women were collected, and amniotic fluid samples of the twins were collected separately. Chromosomal karyotyping analysis and single nucleotide polymorphism array (SNP array) assay were carried out. RESULTS: The results of chromosomal karyotyping analysis showed that 5 of the MCDA twins had inconsistent chromosome karyotypes, with an incidence of 3.4% (5/148). SNP array assay showed that 3 fetuses were mosaics. CONCLUSION: Genetic discordance occurs among MCDA twins, and prenatal counseling for such cases should be given by doctors with experience in medical genetics and fetal medicine, and personalized clinical management should be recommended.

Prenatal diagnosis of type A fetal interrupted aortic arch by four-dimensional echocardiography with HD-flow STIC: A case report.

Interrupted aortic arch (IAA) is a rare complex congenital heart disease characterized by interrupted continuity between ascending aorta and descending aorta. Prenatal diagnosis of IAA by echocardiography is not uncommonly reported despite its rarity. However, employing four-dimensional ultrasound HD-flow imaging and spatiotemporal image correlation (STIC) in diagnosis of this condition has seldom been reported. We report a case of fetal IAA prenatally diagnosed by two-dimensional echocardiography and HD-flow STIC.

BRD4 Inhibition Protects Against Myocardial Ischemia/Reperfusion Injury by Suppressing Inflammation and Oxidative Stress Through the PI3K/AKT Signaling Pathway.

ABSTRACT: This study aims to investigate the effect and the related mechanisms of bromodomain-containing protein 4 (BRD4) inhibition on myocardial ischemia/reperfusion (I/R) injury. In vivo and in vitro myocardial I/R models were constructed. Expression of BRD4 was examined by RT-qPCR and Western blot. I/R injury was evaluated by analyzing cardiac function and the activity of biochemical markers of myocardial injury. Inflammation and oxidative stress were determined by measuring the levels of myeloperoxidase, TNF-α, IL-6, malondialdehyde, and superoxide dismutase. The activation of the PI3K/AKT signaling pathway was tested by the phosphorylation of p85 and AKT. We found BRD4 was significantly increased in the myocardial tissues after myocardial I/R injury. BRD4 inhibition suppressed the indices of cardiac function and the biochemical markers of myocardial injury. I/R-induced inflammation and oxidative stress were suppressed by shBRD4 in vivo and in vitro. In addition, BRD4 inhibition significantly increased the relative protein expression levels of p-p85, p-AKT T308, and p-AKT S473. In conclusion, this study for the first time demonstrated the protective effect of BRD4 inhibition on myocardial I/R injury in vivo and in vitro, and this effect was related to the suppression of inflammation and oxidative stress through the activation of the PI3K/AKT signaling pathway.

Fetal growth velocity references from a Chinese population-based fetal growth study.

BACKGROUND: Fetal growth velocity standards have yet to be established for the Chinese population. This study aimed to establish such standards suitable for the Chinese population. METHODS: We performed a multicenter, population-based longitudinal cohort study including 9075 low-risk singleton pregnant women. Data were collected from the clinical records of 24 hospitals in 18 provinces of China. Demographic characteristics, reproductive history, fetal ultrasound measurements, and perinatal outcome data were collected. The fetal ultrasound measurements included biparietal diameter (BPD), abdominal circumference (AC), head circumference (HC), and femur diaphysis length (FDL). We used linear mixed models with cubic splines to model the trajectory of four ultrasound parameters and estimate fetal weight. Fetal growth velocity was determined by calculating the first derivative of fetal size curves. We also used logistic regression to estimate the association between fetal growth velocities in the bottom 10th percentile and adverse perinatal outcomes. RESULTS: Fetal growth velocity was not consistent over time or among individuals. The estimated fetal weight (EFW) steadily increased beginning at 12 gestational weeks and peaked at 35 gestational weeks. The maximum velocity was 211.71 g/week, and there was a steady decrease in velocity from 35 to 40 gestational weeks. The four ultrasound measurements increased in the early second trimester; BPD and HC peaked at 13 gestational weeks, AC at 14 gestational weeks, and FDL at 15 gestational weeks. BPD and HC also increased from 19 to 24 and 19 to 21 gestational weeks, respectively. EFW velocity in the bottom 10th percentile indicated higher risks of neonatal complications (odds ratio [OR] = 2.23, 95% confidence interval [CI]: 1.79-2.78) and preterm birth < 37 weeks (OR = 3.68, 95% CI: 2.64-5.14). Sensitivity analyses showed that EFW velocity in the bottom 10th percentile was significantly associated with more adverse pregnancy outcomes for appropriate-for-gestational age neonates. CONCLUSIONS: We established fetal growth velocity curves for the Chinese population based on real-world clinical data. Our findings demonstrated that Chinese fetal growth patterns are somewhat different from those of other populations. Fetal growth velocity could provide more information to understand the risk of adverse perinatal outcomes, especially for appropriate-for-gestational age neonates.

Study on the correlation between the ultrasound phenotype and copy number variation of abnormal embryo in spontaneous abortion.

OBJECTIVE: This study aimed to explore the correlation between the ultrasound phenotype and copy number variation (CNV) of abnormal embryos in spontaneous abortion by investigating the abnormal chromosome copy number of embryos at different developmental stages in early spontaneous abortion. METHODS: A total of 539 patients who had early spontaneous abortion in our hospital between 2015 and 2019 were divided into seven groups according to the phenotype of abnormal embryonic development during pregnancy, and the embryonic tissues of the patients were subjected by single nucleotide polymorphism (SNP) microarray. RESULTS: Among 377 cases with abnormal CNV, 295 (78.25%) cases had chromosome trisomy, and 28 (7.43%) cases had a combination of more than two chromosomes. Triploidy, tetraploidy, chromosome microdeletion/duplication, uniparental disomy, and monosomy 45,X were found in 32 (8.48%), five (1.32%), 31 (8.22%), four (1.02%), and eight (2.12%) cases, respectively. Two (0.53%) cases had autosomal chromosome 21 monosomy. Normal karyotype had the highest proportion in the empty sac group; trisomy 16 accounted for the bulk of chromosomes in the normal yolk sac group, complex triploidy occupied the most part in the abnormal yolk sac group, and no remarkable difference in chromosomal abnormality proportion was found between the normal and abnormal yolk sac groups; the most frequent chromosomal anomaly in a group of germ without cardiac activity and germ<5 mm was trisomy 16; triploidy was the most common in the group with 5 mm ≤ germ ≤ 15 mm, whereas the main distribution of chromosome karyotype was normal, followed by trisomy 13 in a group with germ>15 mm. CONCLUSION: Abnormal embryos with different ultrasound phenotypes in early spontaneous abortion have various CNV types and characteristic distribution. Thus, ultrasound combined with SNP array can provide a basis for the etiological analysis of embryos in spontaneous abortion.

Chinese newborn screening for the incidence of G6PD deficiency and variant of G6PD gene from 2013 to 2017.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common X-linked enzymopathies caused by G6PD gene variant. We aimed to provide the characteristics of G6PD deficiency and G6PD gene variant distribution in a large Chinese newborn screening population. We investigated the prevalence of G6PD in China from 2013 to 2017. Then, we examined G6PD activity and G6PD gene in representative Chinese birth cohort to explore the distribution of G6PD gene variant in 2016. We then performed multicolor melting curve analysis to classify G6PD gene variants in 10,357 neonates with activity-confirmed G6PD deficiency, and DNA Sanger sequencing for G6PD coding exons if hot site variants were not found. The screened population, organizations, and provinces of G6PD deficiency were increased from 2013 to 2017 in China. The top five frequency of G6PD gene variants were c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, and c.871G>A and varied in different provinces, with regional and ethnic features, and four pathogenic variant sites (c.152C>T, c.290A>T, c.697G>C, and c.1285A>G) were first reported. G6PD deficiency mainly occurs in South China, and the frequency of G6PD gene variant varies in different regions and ethnicities.

The expression and biological function of chemokine CXCL12 and receptor CXCR4/CXCR7 in placenta accreta spectrum disorders.

OBJECTIVES: Investigation of mechanism related to excessive invasion of trophoblast cells in placenta accreta spectrum disorders (PAS) provides more strategies and ideas for clinical diagnosis and treatment. MATERIALS AND METHODS: Blood and placental samples were collected from included patients. The distribution and expression of CXCL12, CXCR4 and CXCR7 proteins in the paraffin of placental tissue in the included cases were analysed, and we analyse the downstream pathways or key proteins involved in cell invasion. RESULTS: Firstly, our results determined that CXCL12 and CXCR4/CXCR7 were increased in extravillous trophoblastic cell (CXCL12: P < .001; CXCR4: P < .001; CXCR7: P < .001), and the expression levels were closely related to the invasion depth of trophoblastic cells. Secondly, CXCL12 has the potential to become a biochemical indicator of PAS since the high expression of placental trophoblast CXCL12 may be an important source of blood CXCL12. Using lentivirus-mediated RNA interference and overexpression assay, it was found that both chemokine CXCL12 and receptor CXCR4/CXCR7 are associated with regulation of trophoblast cell proliferation, migration and invasion. Further results proved that through the activating the phosphorylation and increasing the expression of MLC and AKT proteins in the Rho/rock, PI3K/AKT signalling pathway, CXCL12, CXCR4 and CXCR7 could up-regulate the expression of RhoA, Rac1 and Cdc42 proteins to promote the migration and invasion of extravillous trophoblastic cell and ultimately formate the placenta accrete compare to the normal placenta. CONCLUSIONS: Our research proved that trophoblasts may contribute to a PAS-associated increase in CXCL12 levels in maternal blood. CXCL12 is not only associated with biological roles of PAS, but may also be potential for prediction of PAS.

Vascular ring and sling in a fetus who developed esophageal and airway compression after birth.

Vascular ring and sling are congenital anomalies of the vascular structure in the thorax with a prevalence of 2.4/10,000 live births. Double aortic arch (DAA), right aortic arch with left ductus arteriosus and aberrant left subclavian artery (RAA-ALSA), and pulmonary artery sling (PAS) are the three common types of vascular ring and sling. These anomalies can be isolated or accompanied by intracardiac malformation. The presence of both vascular ring and PAS is extremely rare. Here, we report a fetus who was prenatally diagnosed with PAS and RAA-ALS, and developed symptoms due to esophageal and airway compression after birth.

[Genetic testing and pregnancy outcome of 337 fetuses with urinary system anomalies].

OBJECTIVE: To explore the genetic basis and pregnancy outcome of fetuses with urinary system anomalies. METHODS: Ultrasonographic features, genetic testing and pregnancy outcomes of 337 fetuses with urinary system anomalies identified by prenatal ultrasonograhy were collected for analysis. RESULTS: Ultrasonographic features of the fetuses were mainly characterized by hydronephrosis or hydronephrosis, polycystic kidney disease, and renal dysplasia. Thirty four fetuses (10.1%) were found to harbor a genetic defect, including 14 numerical chromosomal disorders, 10 structural chromosomal aberrations, and 10 pathogenic copy number variations (CNVs). In 31 cases, the parents elected induced labor. For the 303 fetuses with negative findings, 142 were born by spontaneous delivery or Caesarean section, 48 cases underwent induced labor, 1 case had miscarriage, and the remaining 112 cases had unknown or missed pregnancy outcomes. CONCLUSION: Hydronephrosis or hydronephrosis, polycystic kidney disease, and renal dysplasia are the most common findings among fetuses with urinary system anomalies. Approximately 10.1% of such fetuses are positive by genetic testing.

The prevalence and molecular characterization of (뫧)0 -thalassemia and hereditary persistence of fetal hemoglobin in the Chinese Zhuang population.

OBJECTIVE: To reveal the prevalence and molecular characterization of (δß)0 -thalassemia [(δß)0 -thal] and hereditary persistence of fetal hemoglobin (HPFH) in the Chinese Zhuang population. METHODS: A total of 105 subjects with fetal hemoglobin (Hb F) level ≥5% from 14 204 unrelated ones were selected for the study. Multiplex ligation dependent probe amplification was firstly used to analyze dosage changes of the ß-globin gene cluster for associated with (δß)0 -thal and HPFH mutations. The gap polymerase chain reaction was then performed to identify the deletions using the respective flanking primers. Hematologic data were recorded and correlated with the molecular findings. RESULTS: Twenty-one (0.15%) subjects were diagnosed with Chinese G γ(A γδß)0 -thal. Nine (0.06%) were diagnosed with Southeast Asia HPFH (SEA-HPFH) deletion. Seventy-five (0.53%) cases remained uncharacterized. Three genotypes for Chinese G γ(A γδß)0 -thal and SEA-HPFH deletion were identified, respectively. The genotype-phenotype relationships were discussed. CONCLUSION: Our study for the first time demonstrated that (δß)0 and HPFH were not rare events, and molecular characterized G γ(A γδß)0 -thal and HFPH mutations in the Chinese Zhuang population. The findings in our study will be useful in genetic counseling and prenatal diagnostic service of ß-thalassemia in this populations.

The association between four SNPs (rs7482144, rs4671393, rs28384513 and rs4895441) and fetal hemoglobin levels in Chinese Zhuang ß-thalassemia intermedia patients.

Four SNPs (rs7482144, rs4671393, rs28384513 and rs4895441) associated with HbF levels have been identified in different populations worldwide. To explore whether these SNPs modulate HbF expression in Chinese Zhuang population, 436 Chinese Zhuang ß-thalassemia intermedia (ß-TI) patients were divided into high HbF level group (mean HbF=25.5%, n=218) and low group (mean HbF=6.51%, n=218) for genotyping using PCR-HRM method. Results demonstrated that there was a significantly higher minor allele frequency (MAF=34.2%) of rs4895441 (G) in HMIP in high HbF level group than that in low group (MAF=19.8%) (P=0.001, OR=1.73, 95% CI: 1.24-2.57). The cumulative effects of risk genotypes of these loci for patients carrying any combination of 1, 2 or 3 risk genotype had a gradually increased risk of high HbF level phenotype compared to those without the risk genotypes (OR=1.50-9.06, P=0.0008); Gene-gene interaction of rs7842144 and rs4895441 showed the best model with the smallest prediction error (0.4259) and the greatest consistency of coefficient of variation (P=0.01). We concluded that rs4895441, G on HMIP might be a high-risk modifier variant for high HbF level expression, and HBG2, BCL11A and HMIP genes, as HbF quantitative trait loci (QTL) could have a synergistic effect on increasing the HbF level in Chinese Zhuang ß-TI patients.

New Matching Method for Accelerometers in Gravity Gradiometer.

The gravity gradiometer is widely used in mineral prospecting, including in the exploration of mineral, oil and gas deposits. The mismatch of accelerometers adversely affects the measuring precision of rotating accelerometer-based gravity gradiometers. Several strategies have been investigated to address the imbalance of accelerometers in gradiometers. These strategies, however, complicate gradiometer structures because feedback loops and re-designed accelerometers are needed in these strategies. In this paper, we present a novel matching method, which is based on a new configuration of accelerometers in a gravity gradiometer. In the new configuration, an angle was introduced between the measurement direction of the accelerometer and the spin direction. With the introduced angle, accelerometers could measure the centrifugal acceleration generated by the rotating disc. Matching was realized by updating the scale factors of the accelerometers with the help of centrifugal acceleration. Further simulation computations showed that after adopting the new matching method, signal-to-noise ratio improved from -41 dB to 22 dB. Compared with other matching methods, our method is more flexible and costs less. The matching accuracy of this new method is similar to that of other methods. Our method provides a new idea for matching methods in gravity gradiometer measurement.

A Novel α2-Globin Gene Mutation: Hb Debao [α31(B12)Arg→Trp; HBA2: c.94A>T].

We report a novel mutation on the α2-globin gene, Hb Debao [α31(B12)Arg→Trp; HBA2: c.94A>T] detected in a Chinese family. This mutation gives rise to a previously undescribed hemoglobin (Hb) variant that was undetectable by electrophoretic or chromatographic methods. Hb Debao was associated with an α+-thalassemia (α+-thal) deletion [-α3.7 (rightward)] producing a mild phenotype with significant microcytosis and hypochromia, while the combination of this mutation with an α0-thal deletion (--SEA) resulting in a severe form of Hb H (ß4) disease, which is consistent with a thalassemic phenotype associated with the novel mutation.

A Novel Mutation of the α2-Globin Gene Causing α+-Thalassemia: Hb Nanning (HBA2: c.369_370delinsGA).

We report a novel mutation on the α2-globin gene, Hb Nanning (HBA2:c.369_370delinsGA) detected in a Chinese family. This mutation gives rise to a previously undescribed hemoglobin (Hb) variant that was undetectable by various separation techniques. Both carriers of the mutation have mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) values that are below normal, as would be predicted for an α+-thalassemia (α+-thal) patient.

Genetic Variants at BCL11A and HBS1L-MYB loci Influence Hb F Levels in Chinese Zhuang ß-Thalassemia Intermedia Patients.

Increased Hb F levels can ameliorate the symptoms of ß-thalassemia (ß-thal). Due to the genetic heterogenicity of ß-thal, the relationship between genetic variants in modifier genes and Hb F level has been studied in different populations. The Chinese Zhuang has the second largest population in China and has 6.78% prevalence of ß-thal. However, the effects of these single nucleotide polymorphism (SNP) variants on the Hb F levels of ß-thal intermedia (ß-TI) patients in this population have not been reported. To explore the association between modifier loci (ß-globin gene cluster, HBS1L-MYB intergenic region and BCL11A) and Hb F levels in Chinese Zhuang ß-TI patients, 96 unrelated ß-TI patients (50 males and 46 females) with different Hb F levels were recruited and genotyped by mass spectrometry. A total of 13 SNPs were confirmed to be in a significant relationship with Hb F levels in this population. Of these, high-risk genotypes of six Hb F-associated SNPs, rs9376090, rs7776054, rs9399137, rs9389268, rs9402685 in the HBS1L-MYB intergenic region and rs189984760 in the BCL11A locus, showed association with high Hb F levels, especially for SNPs in linkage disequilibrium. One novel Hb F-associated SNP, rs189984760, was identified in our study. Our findings will be of valuable reference for correlation between modifier genes and Hb F in Chinese Zhuang populations and may lead to better understand the modifying mechanisms for ß-thal.

Identification of a Novel ß-Globin Mutation (HBB: C.189_195delTCATGGC) in a Chinese Family.

ß-Thalassemia (ß-thal) is one of the most common genetic disorders worldwide. Molecular characterization of ß-thal is essential for prevention and understanding the biology of the disease. More and more rare and novel mutations are being reported. Here, we report a novel 7 bp deletion at codons 63-65 (HBB: c.189_195delTCATGGC) in exon 2 of the ß-globin gene in a family from Guangxi Province, China. This novel mutation causes a shift in the normal reading frame of the ß-globin coding sequence and created a stop codon at codon 87 in exon 2, which leads to a ß(0)-thal phenotype.

Mammalian Metallothionein-2A and Oxidative Stress.

Mammalian metallothionein-2A (MT2A) has received considerable attention in recent years due to its crucial pathophysiological role in anti-oxidant, anti-apoptosis, detoxification and anti-inflammation. For many years, most studies evaluating the effects of MT2A have focused on reactive oxygen species (ROS), as second messengers that lead to oxidative stress injury of cells and tissues. Recent studies have highlighted that oxidative stress could activate mitogen-activated protein kinases (MAPKs), and MT2A, as a mediator of MAPKs, to regulate the pathogenesis of various diseases. However, the molecule mechanism of MT2A remains elusive. A deeper understanding of the functional, biochemical and molecular characteristics of MT2A would be identified, in order to bring new opportunities for oxidative stress therapy.

DCAF2 regulates the proliferation and differentiation of mouse progenitor spermatogonia by targeting p21 and thymine DNA glycosylase.

DDB1-Cullin-4-associated factor-2 (DCAF2, also known as DTL or CDT2), a conserved substrate recognition protein of Cullin-RING E3 ligase 4 (CRL4), recognizes and degrades several substrate proteins during the S phase to maintain cell cycle progression and genome stability. Dcaf2 mainly expressed in germ cells of human and mouse. Our study found that Dcaf2 was expressed in mouse spermatogonia and spermatocyte. The depletion of Dcaf2 in germ cells by crossing Dcaf2fl/fl mice with stimulated by retinoic acid gene 8(Stra8)-Cre mice caused a reduction in progenitor spermatogonia and differentiating spermatogonia, eventually leading to the failure of meiosis initiation and male infertility. Further studies showed that depletion of Dcaf2 in germ cells caused abnormal accumulation of the substrate proteins, cyclin-dependent kinase inhibitor 1A (p21) and thymine DNA glycosylase (TDG), decreasing of cell proliferation, increasing of DNA damage and apoptosis. Overexpression of p21 or TDG attenuates proliferation and increases DNA damage and apoptosis in GC-1 cells, which is exacerbated by co-overexpression of p21 and TDG. The findings indicate that DCAF2 maintains the proliferation and differentiation of progenitor spermatogonia by targeting the substrate proteins p21 and TDG during the S phase.

Prenatal chromosomal microarray analysis and karyotyping in fetuses with isolated choroid plexus cyst: A retrospective case-control study.

OBJECTIVES: To evaluate the the diagnostic yield of chromosomal microarray analysis (CMA) in fetuses with isolated CPC (iCPC). METHODS: A total of 315 fetuses with iCPC (iCPC group) and 364 fetuses without abnormal ultrasound findings (control group) were recruited between July 2014 to March 2018. RESULTS: The overall diagnostic yield of chromosomal abnormalities by CMA and karyotyping in iCPC group was up to 4.1 %, higher than 1.4 % in the control group, p < 0.05. The detection rate of pathogenic or likely pathogenic copy number variants (CNVs) with clinical significance by CMA in iCPC group (1.3 %) was higher than in control group (0 %), p < 0.05. According to the type of chromosome abnormalities, the missed diagnosis rate of non-invasive prenatal testing (NIPT) was 1.6 % in our study. CONCLUSIONS: The presence of iCPC on ultrasound examination suggests a potential indication for genetic counseling. Karyotyping and chromosomal microarray analysis may be considered for fetuses with iCPC. It is important to be aware of the limitations of non-invasive prenatal testing, as there is a possibility of residual risk.