Association of prepregnancy body mass index and gestational weight gain trajectory with adverse pregnancy outcomes-a prospective cohort study in Shanghai.

OBJECTIVES: The objective was to investigate the associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) trajectories with adverse pregnancy outcomes (APOs). DESIGN: This was a prospective cohort study. SETTING: This study was conducted in Shanghai Pudong New Area Health Care Hospital for Women and Children, Shanghai, China. PRIMARY AND SECONDARY OUTCOME MEASURES: A cohort study involving a total of 2174 pregnant women was conducted. Each participant was followed to record weekly weight gain and pregnancy outcomes. The Institute of Medicine classification was used to categorise prepregnancy BMI, and four GWG trajectories were identified using a latent class growth model. RESULTS: The adjusted ORs for the risks of large for gestational age (LGA), macrosomia, gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) were significantly greater for women with prepregnancy overweight/obesity (OR=1.77, 2.13, 1.95 and 4.24; 95% CI 1.3 to 2.42, 1.32 to 3.46, 1.43 to 2.66 and 2.01 to 8.93, respectively) and lower for those who were underweight than for those with normal weight (excluding HDP) (OR=0.35, 0.27 and 0.59; 95% CI 0.22 to 0.53, 0.11 to 0.66 and 0.36 to 0.89, respectively). The risk of small for gestational age (SGA) and low birth weight (LBW) was significantly increased in the underweight group (OR=3.11, 2.20; 95% CI 1.63 to 5.92, 1.10 to 4.41; respectively) compared with the normal-weight group; however, the risk did not decrease in the overweight/obese group (p=0.942, 0.697, respectively). GWG was divided into four trajectories, accounting for 16.6%, 41.4%, 31.7% and 10.3% of the participants, respectively. After adjustment for confounding factors, the risk of LGA was 1.54 times greater for women in the slow GWG trajectory group than for those in the extremely slow GWG trajectory group (95% CI 1.07 to 2.21); the risk of SGA and LBW was 0.37 times and 0.46 times lower for women in the moderate GWG trajectory group and 0.14 times and 0.15 times lower for women in the rapid GWG trajectory group, respectively; the risk of macrosomia and LGA was 2.65 times and 2.70 times greater for women in the moderate GWG trajectory group and 3.53 times and 4.36 times greater for women in the rapid GWG trajectory group, respectively; and the women in the other three trajectory groups had a lower risk of GDM than did those in the extremely slow GWG trajectory group, but there was not much variation in the ORs. Notably, different GWG trajectories did not affect the risk of HDP. CONCLUSIONS: As independent risk factors, excessively high and low prepregnancy BMI and GWG can increase the risk of APOs.

[Analysis and clinical application of preimplantation genetic testing for monogenic disorders in a case with Spinal muscular atrophy "2+0" genotype].

OBJECTIVE: To explore the clinical application of preimplantation genetic testing for monogenic disorders (PGT-M) in an unique case with Spinal muscular atrophy (SMA) type 2+0. METHODS: A special SMA family presented at the Third Affiliated Hospital of Guangzhou Medical University on October 19, 2020 was selected as the study subject. Multiple ligation-dependent probe amplification (MLPA) and molecular tagging linkage analysis were carried out to identify the SMN1 genotype of the couple and their fetus. Subsequently, next-generation sequencing (NGS), molecular tagging linkage analysis, and chromosomal microarray analysis were employed to determine the haplotypes and validate the result of PGT-M on the 11 embryos derived for the couple. RESULTS: The female partner was identified as a carrier of the rare SMN1[2+0] variant, and prenatal diagnosis confirmed the fetus to be affected by SMA. Ultimately, PGT-M has successfully selected four embryos free from the pathogenic SMN1 variants and X chromosome deletion. CONCLUSION: PGT-M can effectively prevent the transmission of rare genetic variants such as the SMA 2+0 subtype in the families. Above finding has provided guidance for genetic counseling and family planning for the couple.

Preimplantation genetic testing as a means of preventing hereditary congenital myasthenic syndrome caused by RAPSN.

BACKGROUND: Congenital myasthenic syndrome is a heterogeneous group of inherited neuromuscular transmission disorders. Variants in RAPSN are a common cause of CMS, accounting for approximately 14%-27% of all CMS cases. Whether preimplantation genetic testing for monogenic disease (PGT-M) could be used to prevent the potential birth of CMS-affected children is unclear. METHODS: Application of WES (whole-exome sequencing) for carrier testing and guidance for the PGT-M in the absence of a genetically characterized index patient as well as assisted reproductive technology were employed to prevent the occurrence of birth defects in subsequent pregnancy. The clinical phenotypes of stillborn fetuses were also assessed. RESULTS: The family carried two likely pathogenic variants in RAPSN(NM_005055.5): c.133G>A (p.V45M) and c.280G>A (p.E94K). And the potential birth of CMS-affected child was successfully prevented, allowing the family to have offspring devoid of disease-associated variants and exhibiting a normal phenotype. CONCLUSION: This report constitutes the first documented case of achieving a CMS-free offspring through PGT-M in a CMS-affected family. By broadening the known variant spectrum of RAPSN in the Chinese population, our findings underscore the feasibility and effectiveness of PGT-M for preventing CMS, offering valuable insights for similarly affected families.

Do women's working hours inputs yield higher household economic welfare than men's?

Time allocation, which encompasses various aspects of the labor market and the household sphere, is a key factor affecting both genders in the employment and household spheres. Using the data from China Family Panel Studies Survey (CFPS) of 2014, 2016 and 2018, the paper examines the impact of working hours input on household economic welfare. The research results indicate that women's working hours input significantly contributes to the household economy and passes a series of robustness tests; the positive effect of women's working hours input on the household economy is stronger than that of men using the household savings rate to measure household economic welfare; and there are increasing working hours input and enhancing household economic welfare through the mechanism of increasing household income. Theoretically, time allocation is placed within the logical framework of the household microcosm. It suggests that individual working hours influence household economic welfare. Practically, the research findings provide useful policy insights: raising workers' wage levels, narrowing the gender labor gap, and improving working time systems and work arrangements to promote the equal development of both genders in the employment and household spheres.

Is Chemerin Associated with Gestational Diabetes Mellitus? A Case-Control Study.

Purpose: The aim of this study was to investigate the relationship between gestational diabetes mellitus (GDM) and Chemerin by analyzing chemerin levels in peripheral blood and cord blood, and chemerin mRNA and its protein expression in placenta and adipose tissue. Methods: A case-control study was conducted in 110 women with GDM and 110 controls without GDM who received regular prenatal services and delivered at Shanghai Pudong New Area Healthcare Hospital for Women and Children from June 2019 to December 2020. Results: The age, pre-pregnancy weight, pre-pregnancy BMI, antepartum BMI, TG/HDL ratio and TG levels in pregnant women with GDM were significantly higher than those in women without GDM, and HDL levels were significantly lower than those in the normal group. Chemerin in the umbilical cord blood of the GDM group was significantly higher than in that of the normal group, but there was no difference in chemerin levels in peripheral blood. In the two groups, the chemerin concentration in peripheral blood was significantly higher than that in umbilical cord blood (P<0.001). The Chemerin mRNA and protein expression levels in the placenta and adipose tissue of pregnant women in the GDM group were significantly higher than those in the normal group (P <0.001). In the GDM group, the expression of chemerin protein in adipose tissue was significantly higher than that in placental tissue. Regression analysis showed that the expression level of chemerin protein in placental tissue and adipose tissue was positively correlated with the risk of GDM. Conclusion: Elevated chemerin is closely related to the risk of GDM, and the placenta may be an important secretion of chemotactic factor sources in addition to adipose tissue and participate in the development of GDM.

F8 gene inversion and duplication cause no obvious hemophilia A phenotype.

Hemophilia A (HA, OMIM#306700) is an X-linked recessive bleeding disorder caused by the defects in the F8 gene, which encodes coagulation factor VIII (FVIII). Intron 22 inversion (Inv22) is found in about 45% of patients with severe hemophilia A. Here, we reported a male without obvious hemophilia A phenotype but bearing an inherited segmental variant duplication encompassing F8 as well as Inv22. The duplication was approximately 0.16 Mb and involved from exon 1 to intron 22 of F8. This partial duplication and Inv22 in F8 was first found in the abortion tissue of his older sister with recurrent miscarriage. The genetic testing of his family revealed that his phenotypically normal older sister and mother also had this heterozygous Inv22 and a 0.16 Mb partial duplication of F8, while his father was genotypically normal. The integrity of the F8 gene transcript was verified by sequencing of the adjacent exons at the inversion breakpoint, which explained why this male had no phenotype for hemophilia A. Interestingly, although he had no significant hemophilia A phenotype, the expression of C1QA in his mother, sister, and the male subject was only about half of that in his father and normal population. Our report broadens the mutation spectrum of F8 inversion and duplication and its pathogenicity in hemophilia A.

Case Report: A Paternal 20q13.2-q13.32 Deletion Patient With Growth Retardation Improved by Growth Hormone.

Interstitial chromosome 20q deletions, containing GNAS imprinted locus, are rarely reported in the past. Hereby, we presented a Chinese boy with a novel 4.36 Mb deletion at paternal 20q13.2-13.32, showing feeding difficulty, malnutrition, short stature, lower limb asymmetry, sightly abnormal facial appearance and mild intellectual abnormality. With 3 years' growth hormone treatment, his height was increased from 90 to 113.5 cm. This report is the first time to describe the outcome of clinical treatment on a patient with this rare chromosomal 20 long arm interstitial deletion, containing GNAS locus, which may facilitate the diagnosis and treatment of this type of patient in the future.

Comprehensive copy number analysis of Y chromosome-linked loci for detection of structural variations and diagnosis of male infertility.

Infertility affects about 15% of heterosexual couples and male factors account for ~45-50% of clinical cases. Genetic factors play an important role in male infertility and thus we try to develop a cost-effective method for screening the genetic factors in male infertility. In our retrospective proof-of-concept study, we employed the high-throughput ligation-dependent probe amplification (HLPA) to examine the copy number by 115 genomic loci covering the Y chromosome, and 5 loci covering the X chromosome-specific region. We identified 8 sex chromosome aneuploid people from the low sperm concentration (LSC) group, and Y chromosome-specific microdeletion/duplications in 211 samples from the LSC group, and in 212 samples from the control group. 35 samples showed complete loss of AZFc (BPY2 to CDY1B deletion), which was not observed in controls. Nevertheless, a partial loss of AZFc (BPY2 to BPY2B deletion) was detected at comparable frequencies in both groups (68/211 vs. 108/212, respectively). And we further found structural variations in 28.6 and 26.9% samples from infertility and fertility groups. Moreover, we found that there were lower copy numbers for heterochromatic sequences in men with LSC. Especially, we reported that ultra-low relative copy number (RCN) (<0.5) type and low RCN (0.5 to <0.75) type in Yq12 were more often in the LSC group for the first time. Our results not only shed light on the potential role of low RCN in Yq12 in male infertility but also showed that HLPA can be a powerful and cost-effective tool for clinical screening in male infertility.

Study on energy saving and environmental protection generator with hydrogen-oxygen-gasoline compound fuel.

The generator is the most popular mobile power device and backup power device in the world. It is very important for human life. Therefore, it is important to develop more efficient combustion technology in order to save energy and reduce air pollution. In this paper, a novel technology of hydrogen and oxygen compound gasoline fuel is developed. Hydrogen and oxygen gases are produced from an electrolytic cell and then mixed with the intake gasoline and air. The compound fuel is sucked into the engine combustion chamber. The hydrogen and oxygen gases can be produced immediately without any storage device of hydrogen. The experimental results show that this technology can increase the power generation and decrease emission pollution due to promoting combustion efficiency. In addition, the spark plug seat temperature increases due to higher heat value of hydrogen. This technique can reduce carbon monoxide and HC, but increase carbon dioxide. The research and development of this technique can achieve the goals of energy saving, emission reduction, relative safety, easy refitting and low refitting expense. Moreover, this research possesses academic innovation and industrial application.

Impact of long working hours on health based on observations in China.

BACKGROUND: Health should be a key focus in considerations of long working hours. Little is known about for which groups of people working longer hours is more harmful to their health. Additionally, the definition of long working hours varies slightly due to country differences in working hours systems. Therefore, this study aims to explore the association between long working hours and the self-rated health (SRH) level, taking into account gender and educational differences. METHOD: Data were collected from two waves (2016 and 2018) of the China Family Panel Studies (CFPS). A total of 6972 workers were available for analysis. Descriptive statistical analysis, an ordered probit (oprobit) model and conditional mixed process (CMP) regression analyses were used to analyze the data. Furthermore, I conducted a stratified analysis by gender and education groups. RESULT: This study observed a negative association between long working hours and SRH. Compared to other education groups, labor with long working hours had a more negative impact on the SRH of those with higher education. Long working hours had a more negative influence on the SRH of male workers. In contrast, no clear association was found among female workers. CONCLUSION: This study estimates SRH of those with long working hours in China. Among workers, long working hours have a negative impact on the health of workers with college degrees or beyond. One possible explanation is that they do not exercise, their diet is unreasonable, and their working conditions involve chronic exposure to computer radiation. The negative health effects of long working hours on males are four times greater than those on females. This study provides valuable insights into the health of the workforce, working time regulations and overtime rules.

Cardiac Na+-Ca2+ exchanger 1 (ncx1h) is critical for the ventricular cardiomyocyte formation via regulating the expression levels of gata4 and hand2 in zebrafish.

Ca2+ signaling is critical for heart development; however, the precise roles and regulatory pathways of Ca2+ transport proteins in cardiogenesis remain largely unknown. Sodium-calcium exchanger 1 (Ncx1) is responsible for Ca2+ efflux in cardiomyocytes. It is involved in cardiogenesis, while the mechanism is unclear. Here, using the forward genetic screening in zebrafish, we identified a novel mutation at a highly-conserved leucine residue in ncx1 gene (mutantLDD353/ncx1hL154P) that led to smaller hearts with reduced heart rate and weak contraction. Mechanistically, the number of ventricular but not atrial cardiomyocytes was reduced in ncx1hL154P zebrafish. These defects were mimicked by knockdown or knockout of ncx1h. Moreover, ncx1hL154P had cytosolic and mitochondrial Ca2+ overloading and Ca2+ transient suppression in cardiomyocytes. Furthermore, ncx1hL154P and ncx1h morphants downregulated cardiac transcription factors hand2 and gata4 in the cardiac regions, while overexpression of hand2 and gata4 partially rescued cardiac defects including the number of ventricular myocytes. These findings demonstrate an essential role of the novel 154th leucine residue in the maintenance of Ncx1 function in zebrafish, and reveal previous unrecognized critical roles of the 154th leucine residue and Ncx1 in the formation of ventricular cardiomyocytes by at least partially regulating the expression levels of gata4 and hand2.

ARHGEF12 regulates erythropoiesis and is involved in erythroid regeneration after chemotherapy in acute lymphoblastic leukemia patients.

Hematopoiesis is a finely regulated process in vertebrates under both homeostatic and stress conditions. By whole exome sequencing, we studied the genomics of acute lymphoblastic leukemia (ALL) patients who needed multiple red blood cell (RBC) transfusions after intensive chemotherapy treatment. ARHGEF12, encoding a RhoA guanine nucleotide exchange factor, was found to be associated with chemotherapy-induced anemia by genome-wide association study analyses. A single nucleotide polymorphism (SNP) of ARHGEF12 located in an intron predicted to be a GATA1 binding site, rs10892563, is significantly associated with patients who need RBC transfusion (P=3.469E-03, odds ratio 5.864). A luciferase reporter assay revealed that this SNP impairs GATA1-mediated trans-regulation of ARHGEF12, and quantitative polymerase chain reaction studies confirmed that the homozygotes status is associated with an approximately 61% reduction in ARHGEF12 expression (P=0.0088). Consequently, erythropoiesis was affected at the pro-erythroblast phases. The role of ARHGEF12 and its homologs in erythroid differentiation was confirmed in human K562 cells, mouse 32D cells and primary murine bone marrow cells. We further demonstrated in zebrafish by morpholino-mediated knockdown and CRISPR/Cas9-mediated knockout of arhgef12 that its reduction resulted in erythropoiesis defects. The p38 kinase pathway was affected by the ARHGEF12-RhoA signaling in K562 cells, and consistently, the Arhgef12-RhoA-p38 pathway was also shown to be important for erythroid differentiation in zebrafish as active RhoA or p38 readily rescued the impaired erythropoiesis caused by arhgef12 knockdown. Finally, ARHGEF12-mediated p38 activity also appeared to be involved in phenotypes of patients of the rs10892563 homozygous genotype. Our findings present a novel SNP of ARHGEF12 that may involve ARHGEF12-RhoA-p38 signaling in erythroid regeneration in ALL patients after chemotherapy.

A Misalignment Optical Guiding Module for Power Generation Enhancement of Fixed-Type Photovoltaic Systems.

: This study presents a misalignment light-guiding module to increase the effectiveness of absorbing light. For a general fixed-type photovoltaic (PV) panel, the misalignment light decreases the efficiency of the system. A solar tracking system was installed for obtaining higher power generation. However, the cost of the PV system and maintenance was 5-10 times higher than the general type. In this study, this module is composed of an array of misalignment light-guiding units that consist of a non-axisymmetric compound parabolic curve (NACPC) and a freeform surface collimator. The NACPC efficiently collects the misalignment light within ±30° and guides the light to the collimator. The light has a better uniformity and smaller angle at the exit aperture. The simulation results show that the optical efficiency of the unit was above 70% when the misalignment angle was smaller than 20°. The experimental results show that the power generation of the light-guiding unit was 1.8 times higher than the naked PV panel.

[Effect of CYP11B2 gene -344T/C polymorphism on renin-angiotensin-aldosterone system activity and blood pressure response to hydrochlorothiazide].

OBJECTIVE: To evaluate the effect of CYP11B2 gene -344T/C polymorphism on renin-angiotensin-aldosterone system (RAAS) activity and blood pressure in response to hydrochlorothiazide (HCTZ) treatment in Han Chinese patients with essential hypertension. METHODS: Eight hundred and twenty-nine patients with mild/moderate essential hypertensive were enrolled. All subjects had their antihypertensive medications withdrawn. After two weeks of wash-out period with placebo, each patient was given 12.5 mg of HCTZ per day for the next six weeks. Physical, biochemical measurements, and the activity of RAAS were taken at the end of the wash-out period (baseline) and 6-week diuretic therapy period. Changes in systolic and diastolic blood pressure were analyzed for association with interaction between genotypes at CYP11B2 -344T/C polymorphism and gender. RESULTS: A total of 776 patients completed the study. 17.5% of subjects have achieved blood pressure normalization after six weeks treatment. For male patients, the aldosterone level with CC genotype was significantly higher than that of those with TT or TC genotype. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was less obvious than that in others, whilst the increase of aldosterone level was greater. For female patients, no association was found between CYP11B2 -344T/C polymorphism and aldosterone level. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was greater than others, whilst the increase of aldosterone activity was less apparent. CONCLUSION: In males, the -344T/C polymorphism of CYP11B2 gene is associated with aldosterone level, and the change of aldosterone level was greater, the blood pressure response was weaker after HCTZ treatment. In females, there was no association between this polymorphism and aldosterone level. The change of aldosterone level and blood pressure response to HCTZ were different from that in males.