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To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) in functional gastrointestinal disorders (FGIDs) in children with abdominal bloating and changes in their gut microbiome and metabolome.Twelve pediatric FGID patients with predominant abdominal bloating who underwent FMT were enrolled in the study. Fourteen healthy controls and four stool donors were included for analysis. Clinical responses were assessed at 8 weeks after FMT. Fecal bacterial composition was determined by 16S rRNA gene sequencing. The fecal metabolome was measured by targeted metabolomics analysis.Median age of the 12 children with FGIDs was 6 years, and nine were boys. Abdominal bloating was relieved in all patients by FMT at 8 weeks. Meanwhile, FMT significantly improved abdominal pain and diarrhea. The a diversity was significantly lower in the FGID patients, while the fecal microbial community (β diversity) separated from that of healthy control (HCs). The relative abundances of multiple bacterial genera were significantly changed in the feces of the pediatric FGID patients. The levels of several short-chain fatty acids were lower, and lactic acid level was higher in FGID patients than in HCs. Altered bacterial composition was correlated with changes in the fecal metabolite profile and clinical symptoms in FGID patients. FMT modulated fecal microbiome and metabolome in FGID children toward a healthy state.FMT relieves abdominal bloating and modulates fecal microbiome and metabolome toward a healthy state in children with FGIDs. FMT may provide an alternative therapy for children with FGIDs and abdominal bloating.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stromal cells that have a critical role in the maintenance of skeletal tissues such as bone, cartilage, and the fat in bone marrow. In addition to providing microenvironmental support for hematopoietic processes, BM-MSCs can differentiate into various mesodermal lineages including osteoblast/osteocyte, chondrocyte, and adipocyte that are crucial for bone metabolism. While BM-MSCs have high cell-to-cell heterogeneity in gene expression, the cell subtypes that contribute to this heterogeneity in vivo in humans have not been characterized. To investigate the transcriptional diversity of BM-MSCs, we applied single-cell RNA sequencing (scRNA-seq) on freshly isolated CD271+ BM-derived mononuclear cells (BM-MNCs) from two human subjects. We successfully identified LEPRhiCD45low BM-MSCs within the CD271+ BM-MNC population, and further codified the BM-MSCs into distinct subpopulations corresponding to the osteogenic, chondrogenic, and adipogenic differentiation trajectories, as well as terminal-stage quiescent cells. Biological functional annotations of the transcriptomes suggest that osteoblast precursors induce angiogenesis coupled with osteogenesis, and chondrocyte precursors have the potential to differentiate into myocytes. We also discovered transcripts for several clusters of differentiation (CD) markers that were either highly expressed (e.g., CD167b, CD91, CD130 and CD118) or absent (e.g., CD74, CD217, CD148 and CD68) in BM-MSCs, representing potential novel markers for human BM-MSC purification. This study is the first systematic in vivo dissection of human BM-MSCs cell subtypes at the single-cell resolution, revealing an insight into the extent of their cellular heterogeneity and roles in maintaining bone homeostasis.

(1) Background: Optimal bone mass accumulation during adolescence is crucial for maximising peak bone mass during adulthood. Dietary antioxidant vitamins may contribute to bone mass accumulation. This 2.5-year-long longitudinal study aimed to evaluate the relationships between dietary vitamin A, C, and E intakes and the annual changes in bone parameters among Chinese adolescents. (2) Method: Subjects aged 10–18 years (n = 1418) were recruited from a secondary school in Jiangmen, China. Dietary vitamin A, C, and E intakes were assessed using 24 h dietary records over 3 consecutive days. The Sahara Clinical Bone Sonometer was used to measure the broadband ultrasound attenuation (BUA) and the speed of sound (SOS). Their annual changes were then calculated (i.e., BUA%/year, SOS%/year). The associations were detected after adjusting for the baseline bone phenotype; age; sex; weight; height; pubertal stage; physical activity; and dietary intakes of vitamin D, calcium and energy. (3) Results: A curvilinear relationship was found between the dietary intake of vitamin C and BUA%/year (p = 0.026); further analyses in the subgroups revealed that this relationship was observed in male adolescents (p = 0.012). A positive association was observed only in boys with a dietary vitamin C intake of ≥159.01 mg/day (β = 0.395, p = 0.036). Moreover, a linear positive association was shown between the dietary intake of vitamin E and BUA%/year in female adolescents (β = 0.082, p = 0.033). (4) Conclusion: Our findings indicated that dietary vitamin C intake has a threshold effect on bone mass gain in male adolescents and that dietary vitamin E intake could be a positive predictor of bone mass gain in female adolescents.

Objective We carried out sensitivity analyses on gut microbiota metagenomic sequencing, untargeted metabolome, targeted metabolome for short-chain fatty acids (SCFAs) and human whole genome sequencing from 402 early postmenopausal Chinese women to search for early omics-biomarkers and gain novel insights into the potential mechanisms of BP regulation in postmenopausal women. Methods Clusters of co-abundant gut bacterial species and serum untargeted metabolites were identified by weighted gene co-expression network analysis (WGCNA). Partial least square analysis and joint analysis were performed to detect BP-associated omics-variables. Partial Pearson correlation was conducted to identify the interactions of microbe--host for host BP variation. Mendelian randomization analysis and causal inference test were used to examine causal relationships among gut microbiota, metabolites and BP variation. Results In the present study, 651 bacterial species and 296 metabolites were binned into 53 and 26 co-abundance clusters by WGCNA, respectively. Then, we totally identified four gut bacterial species, one host metabolites and two SCFAs that were significantly associated with both SBP and DBP. Moreover, we found that gut microbiota would play important roles in host metabolic activity. Finally, our results revealed that increased Bacteroides fragilis could elevate BP via decreased caproic acid, and phenylacetylglutamine mediated the causal relationships of both B. fragilis and Clostridium sp.CAG.226 on DBP variation. Conclusion Multi-omics datasets integration has the potential to capture complementary effect and their interactions for BP variation, revealed the potential pathogenesis of BP variation and may be useful for studying other complex diseases/traits.

The zona pellucida (ZP) plays vital roles in reproductive processes including oogenesis, fertilization, and preimplantation development. Both human and rat ZP consist of four glycoproteins, called ZP1, ZP2, ZP3, and ZP4. Our previous research reported a novel Zp1 mutation in cases of human infertility, associated with an abnormal phenotype involving the absence of the ZP. Here, we developed a homologous rat strain to investigate the pathogenic effect. The ovaries of homozygous (Zp1MT/MT) females possessed both growing and fully grown oocytes; the oocytes completely lacked a ZP, but ZP1 was detectable inside the cytoplasm. Only 1–2 eggs were recovered from oviducts of superovulated Zp1MT/MT females, while an average of 21 eggs were recovered from superovulated Zp1WT/WT per female. The eggs of Zp1MT/MT females were not surrounded by a ZP and lost their fertilization capacity in vitro. Zp1MT/MT females mated with wild-type males failed to become pregnant. Studies in 293T cells showed that mutant Zp1 resulted in a truncated ZP1 protein, which might be intracellularly sequestered and interacted with wild-type ZP3 or ZP4. Our results suggest that the Zp1 point mutation led to infertility and loss of the ZP in oocytes in rats.Summary sentenceZp1 mutation can lead to congenital deficiencies and ZP loss, which leads to human infertility. The interaction between truncated ZP1 and ZP3 or ZP4 is gained, which affects their normal transport and secretion, suggesting that normal ZP1 is crucial for the structure of the ZP and for fertility.

Although previous studies have explored the gene expression profiles of human oocytes and granulosa cells by single‐cell RNA sequencing (scRNA‐seq), the dynamic regulatory network at a single‐cell resolution during folliculogenesis remains largely unknown. We identified 10 functional modules by WGCNA, four of which were significantly correlated with primary/antral oocyte and antral/pre‐ovulatory granulosa cells. Functional enrichment analysis showed that the brown module, which was correlated with antral oocyte, was enriched in oocyte differentiation, and two core subnetworks identified by MCODE were involved in cell cycle (blue subnetwork) and oogenesis (red subnetwork). The cell‐specific network (CSN) analysis demonstrated a distinct gene network structure associated with the antral follicular stage, which was notably different from other developmental stages. To our knowledge, this is the first study to explore gene functions during folliculogenesis at single‐cell network level. We uncovered two potential gene subnetworks, which may play an important role in oocyte function beginning at the antral stage, and further established their rewiring process at intra‐network/whole transcriptome level. The findings provide crucial insights from a novel network perspective to be further explored in functional mechanistic studies.

In this study, we investigated a gene-edited (Zp2MT/MT) rat model of infertility caused by the failure to express the zona pellucida glycoprotein 2 (ZP2) due to the significant reduction of mRNA amount. We examined the defects in the zona pellucida (ZP) caused by ZP2 nullification and the influence of these defects on aspects of oocyte development, including apoptosis and fertilization ability. To investigate the cause of the influence to the oocytes’ development, we evaluated the morphology of follicular transzonal projections (TZPs), known as ‘bridges’, which mediate the bidirectional signaling between the oocyte and surrounding granulosa cells and the level of reactive oxygen species (ROS) in ovulated eggs. Our results showed that two types of ZP defects were generated in the Zp2MT/MT rat,that is, ZP intact but thinned and ZP cracked (or even absent). The fertilization rate of the ovulated eggs reduced in both types, while increased oocyte apoptosis was observed only in the latter type. Moreover, the increased oocyte apoptosis rate correlated closely with the reduction in follicular TZPs and increased ROS levels in ovulated egg. In conclusion, nullification of rat ZP2 destroyed the integrity of the ZP, impaired the bidirectional signaling between the oocyte and surrounding granulosa cells. Therefore, the resulting infertility likely occurs via elevation of oxidative stress and oocytes apoptosis.

Objective This study aimed to evaluate the overall effects of hormone therapy (HT) on muscle strength in postmenopausal women through a systematic review and meta-analysis. Methods PubMed, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials were systematically searched from the inception dates to August 2019. Randomized controlled trials (RCTs) that compared the effects of HT with either no therapy or placebo on muscle strength in postmenopausal women were eligible. The quality of studies was assessed using the Cochrane risk of bias tool. Measurements of changes in muscle strength compared to baseline were extracted for pooled analysis. The effect size was calculated as standardized mean differences using a random effects model. Results We identified nine studies with a combined population of 2,476 postmenopausal women. The studies included were assessed to be of good quality overall. The results showed that HT was not associated with muscle strength gain in postmenopausal women (standardized mean difference = 0.352; 95% confidence interval, -0.098 to 0.803; P = 0.125; I = 95.3%). The changes in muscle strength in women receiving HT were not significant. The results were unchanged when stratified by treatment type, muscle group, and treatment duration. Conclusions The use of HT was not associated with the improvement of muscle strength in postmenopausal women. This finding suggested that HT might not improve muscle strength or that the effect size was too small to identify significant therapeutic efficacy.

Background Premature ovarian insufficiency (POI) plagues 1% of women under 40, while quite a few remain an unknown cause. The development of sequencing has helped find pathogenic genes and reveal the relationship between DNA repair and ovarian reserve. Through the exome sequencing, our study targets screening out the possible POI pathogenic gene and variants in a Chinese family and 20 sporadic POI patients, preliminarily exploring the functional impact and finding out potential linkages between the gene and POI. Results The whole exome sequencing suggested a novel FMN2 heterozygous variant c.1949C > T (p.Ser650Leu) carried by all three patients in a Chinese family and another c.1967G > A(p.Arg656His) variant in a sporadic case. Since no FMN2 missense mutation is reported for causing human POI, we preliminarily assessed p.Ser650Leu variant via cross-species alignment and 3D modeling and found it possibly deleterious. A series of functional evidence was consistent with our hypothesis. We proved the expression of FMN2 in different stages of oocytes and observed a statistical difference of chromosomal breakages between the POI patient carrying p.Arg656His variant and the health control (p = 0.0013). Western Blot also suggested a decrease in FMN2 and P21 in the mutant type and an associated increase in H2AX. The p.Arg656His variant with an extremely low frequency also indicated that the gene FMN2 might play an essential role in the genetic etiology of POI. To the best of our knowledge, this is the first POI report on missense variants of FMN2. Conclusion This finding indicates a novel gene possibly related to POI and sheds lights on the study of FMN2.

While the gut microbiome has been reported to play a role in bone metabolism, the individual species and underlying functional mechanisms have not yet been characterized. We conducted a systematic multi-omics analysis using paired metagenomic and untargeted serum metabolomic profiles from a large sample of 499 peri- and early post-menopausal women to identify the potential crosstalk between these biological factors which may be involved in the regulation of bone mineral density (BMD). Single omics association analyses identified 22 bacteria species and 17 serum metabolites for putative association with BMD. Among the identified bacteria, Bacteroidetes and Fusobacteria were negatively associated, while Firmicutes were positively associated. Several of the identified serum metabolites including 3-phenylpropanoic acid, mainly derived from dietary polyphenols, and glycolithocholic acid, a secondary bile acid, are metabolic byproducts of the microbiota. We further conducted a supervised integrative feature selection with respect to BMD and constructed the inter-omics partial correlation network. Although still requiring replication and validation in future studies, the findings from this exploratory analysis provide novel insights into the interrelationships between the gut microbiome and serum metabolome that may potentially play a role in skeletal remodeling processes.

Background: Bone mass acquisition during growth is a major determinant of the risk of developing osteoporosis later in life. Body composition is an anthropometric determinant of bone mineral density (BMD) and significantly influences its development during childhood and adolescence. Objective: This study aimed to systematically examine the association between body composition and bone mineral density in children and adolescents. Methods: Observational studies addressing this association were identified from PubMed (MEDLINE), Embase, Scopus and the Cochrane Library (up to January 2021). The study populations consisted of healthy children and adolescents. The DerSimonian and Laird method was used to compute pooled estimates of effect size and the respective 95% confidence intervals for upper limbs, femoral neck (FN), lumbar spine (LS) and total body, respectively. Subgroup analyses were further performed based on age, sex and ethnicity. Results: Thirty-one published studies were eligible for inclusion in this systematic review and meta-analysis, including three longitudinal studies. The combined population from all the studies amounted to 21,393 (11,205 males and 10,188 females). The pooled estimates of the correlation coefficients for lean mass (LM) and BMD ranged from 0.53 to 0.74 (p < 0.050), and the pooled regression coefficients ranged from 0.23 to 0.79 for FN, LS and total body (p < 0.050). For fat mass (FM), the pooled correlation coefficients ranged from 0.10 to 0.50 (p < 0.050) and the pooled regression coefficient was only significant for FN BMD with a weak strength (pooled β = 0.07, p < 0.050). The pooled regression coefficients for body fat percentage (BF%) were between −0.54 and −0.04 (p < 0.050). The subgroup analysis revealed a stronger association in Asians than in Caucasians for LM and in males compared to females for BF% (p < 0.050). Conclusions: This systematic review and meta-analysis supports a positive association between LM and BMD. BF% appears to have a deleterious effect on bone acquisition in children and adolescents.

Background The optimal time at which to perform a frozen-thawed embryo transfer (FET) following a failed in-vitro fertilization-embryo transfer (IVF-ET) attempt remains elusive to most reproductive experts. Physicians often delay the introduction of FET due to concerns related to potential residual effects of ovarian hyperstimulation which may interfere with the regular menstrual cycle. Moreover, given that most of the published studies on the topic are retrospective and have inconsistent findings, it is crucial to develop evidence-based randomized control guides for clinical practice. Therefore, this well-designed randomized controlled trial (RCT) was conducted to determine whether it is necessary to delay FET for at least one menstrual cycle after the failure of fresh embryo transfer. Methods Infertile women eligible for IVF-ET were invited to participate in this multicenter, randomized, non-inferiority, parallel-group, unblinded, controlled trial at the academic fertility centers of four public hospitals in Chinese Mainland. Infertile women scheduled to receive their first FET cycle after a failed IVF-ET attempt were randomly assigned to either (a) the immediate FET group in which FET was performed in the first menstrual cycle following the failed IVF-ET cycle (n = 366) or (b) the delayed FET group in which FET was performed in the second or subsequent menstrual cycle following the failed IVF-ET cycle (n = 366). All FET cycles were performed during hormone replacement cycles for endometrial preparation. The primary outcome was the ongoing pregnancy, defined as a detectable fetal heart beat beyond twelve weeks of gestation. Secondary outcomes were other pregnancy-related outcomes, maternal and neonatal complications. Analysis was performed by both intention-to-treat and per-protocol principles. Results A total of 646 FETs were completed. The frequency of moderate to severe depression and high stress level prior to FET in delayed FET group were significantly higher than that in immediate FET group (10.6% vs 6.1%, p = 0.039; 30.3% vs 22.4%, p = 0.022, respectively). Immediate FET resulted in a higher frequency of clinical pregnancy than did delayed FET (41.7% vs 34.1%), for a relative risk (RR) of 1.23 (95% confidence interval [CI], 1.00–1.50; p = 0.045). Women who underwent immediate FET also had a lower frequency of biochemical pregnancy loss (11.7% vs. 30.6%), with a RR of 0.28 (95% CI 0.23–0.63, p p = 0.038). Although the ongoing pregnancy and live birth rates did not differ significantly between the immediate FET and delayed FET groups (37.1% vs 30.3%, RR 1.22, 95% CI 0.99–1.52, p = 0.067; 36.5% vs 30.0%, RR 1.22, 95% CI 0.98–1.52, p = 0.079, respectively), a multivariate logistic regression analysis adjusted for potential confounders such as depression and stress levels revealed that the immediate FET group had a significantly higher ongoing pregnancy and live birth rates than the delayed FET group (odds ratio 0.68, 95% CI 0.47–0.99, p = 0.041; odds ratio 0.67, 95% CI 0.46–0.96, p = 0.031). The risks of maternal and neonatal complications were comparable between the two groups. Conclusions In women with a previous failed IVF-ET attempt, immediate FET resulted in higher ongoing pregnancy and live birth rates than delayed FET. These findings warrant caution in the indiscriminate application of a delayed FET strategy when apparent risk of high stress level is perceived. Trial registration ChiCTR2000033313.

AIM Gestational hypertension is a common disorder of pregnancy. This study aims to evaluate the effect of labor induction with dinoprostone vaginal suppositories (Propess) on pregnancy outcomes in pregnant women with gestational hypertension. METHODS The retrospective study included 375 patients with gestational hypertension. All patients were included into three groups according to the characteristics at admission. Women who had initiated labor spontaneously at admission were enrolled in Spontaneous labor group. According to Bishop score, other patients underwent labor induction with Propess or oxytocin were enrolled in Propess group or Oxytocin group. Demographic information and perinatal outcome data were collected. RESULTS The vaginal delivery rate of the women with gestational hypertension was respectively 93.5% (Spontaneous labor group), 77.0% (Propess group), and 52.5% (Oxytocin group) in three groups with significant difference (P

Objective This study aimed to investigate the potential factors that affect the induction to delivery time interval in women undergoing induction of labor with a controlled-release dinoprostone vaginal insert. Methods Pregnant women who presented for delivery at Hubei Maternal and Child Health Hospital from January 2016 to August 2016 were recruited. Finally, 1265 women who underwent labor induction with a vaginal dinoprostone (PGE2) insert were analyzed. Univariate and multivariate linear regression analyses were used to estimate the relevant risks for delivery time. Results Among the1265 subjects, the mean delivery time was 18.92 ± 12.50 hours. Univariate and multivariate analyses showed that fetal weight, an obstetric complication (premature rupture of the membranes), and the delivery history were significantly associated with the induction to delivery time. Biparietal diameter was related to the vaginal delivery time in univariate analysis, but there was no significant difference after adjustment in multivariate analysis. Conclusions Vaginal dinoprostone is an effective method for successful induction of labor. Gestational age, parity, and fetal weight are major factors that predict the induction to delivery time interval.

Objectives: Aiming to uncover the genetic basis of abdominal obesity, we performed a genome-wide association study (GWAS) meta-analysis of trunk fat mass adjusted by trunk lean mass (TFMadj) and followed by a series of functional investigations. Subjects: A total of 11,569 subjects from 6 samples were included into the GWAS meta-analysis. Methods: Meta-analysis was performed by a weighted fixed-effects model. In silico replication analysis was performed in the UK-Biobank (UKB) sample (N=331,093) and in the GIANT study (N up to 110,204). Cis-expression QTL (cis-eQTL) analysis, dual-luciferase reporter assay and electrophoresis mobility shift assay (EMSA) were conducted to examine the functional relevance of the identified SNPs. At last, differential gene expression analysis (DGEA) was performed. Results: We identified an independent SNP rs12409479 at 1p21 (MAF=0.07, p=7.26×10−10), whose association was replicated by the analysis of TFM in the UKB sample (one sided p=3.39×10−3), and was cross-validated by the analyses of BMI (one-sided p=0.03) and WHRadj (one-sided p=0.04) in the GIANT study. Cis-eQTL analysis demonstrated that allele A at rs12409479 was positively associated with PTBP2 expression level in subcutaneous adipose tissue (N=385, p=4.15×10−3). Dual-luciferase reporter assay showed that the region repressed PTBP2 gene expression by downregulating PTBP2 promoter activity (p

Objective Fresh fruit intake has been found to be associated with risk of gestational diabetes mellitus (GDM); however, the evidence is limited and the findings are inconsistent. We aimed to assess the association of fresh fruit intake by fruit subgroups based on their glycemic index (GI) and glycemic load (GL) values and GDM incidence in Chinese pregnant women. Methods We included 3300 eligible women from the Tongji Maternal and Child Health Cohort. Dietary intakes were assessed by using a validated semiquantitative food frequency questionnaire. GDM was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test. In the adjusted logistic regression model, odds ratios and 95% confidence intervals for GDM were computed for the highest compared with lowest quintiles of fruit intake. Results GDM occurred in 378 (11.5%) of 3300 pregnant women. The average fresh fruit consumption was 381.7 g/d. The adjusted odds ratios (95% confidence intervals) for GDM from the lowest to highest quintile of whole fruit consumption were 1.00 (referent), 0.80 (0.56, 1.12), 0.74 (0.52, 1.05), 0.63 (0.44, 0.92), and 0.41 (0.27, 0.62), respectively; Ptrend Conclusions Our findings suggested an inverse association of fresh fruit intake with the risk of GDM in Chinese pregnant women. In women with GDM risk, low GI and GL fresh fruit consumption should be privileged versus those with high GI and GL.

In this paper, a delayed Nicholson's blowflies model with a linear harvesting term is investigated. By transforming the model into an equivalent integral equation, and applying a fixed point theorem inc ones, we establish a sufficient condition which ensure the existence of positive almost periodic solutions for the Nicholson's blowflies model. The results of this paper are completely new and complement those of the previous studies. The approach is new.

Background Increasing evidence suggests that human gut microbiome plays an important role in variation of skeletal muscle mass (SMM). However, specific causal mechanistic relationship of human gut microbiome with SMM remains largely unresolved. Understanding the causal mechanistic relationship may provide a basis for novel interventions for loss of SMM. This study investigated whether human gut microbiome has a causal effect on SMM among Chinese community‐dwelling healthy menopausal women. Methods Estimated SMM was derived from whole‐body dual‐energy X‐ray absorptiometry. We performed integrated analyses on whole‐genome sequencing, shotgun metagenomic sequencing, and serum short‐chain fatty acids (SCFAs), as well as available host SMM measurements among community‐dwelling healthy menopausal women (N = 482). We combined the results with summary statistics from genome‐wide association analyses for human gut microbiome (N = 952) and SMM traits (N = 28 330). As a prerequisite for causality, we used a computational protocol that was proposed to measure correlations among gut metagenome, metabolome, and the host trait to investigate the relationship between human gut microbiome and SMM. Causal inference methods were applied to assess the potential causal effects of gut microbial features on SMM, through one‐sample and two‐sample Mendelian randomization (MR) analyses, respectively. Results In metagenomic association analyses, the increased capacity for gut microbial synthesis of the SCFA butyrate was significantly associated with serum butyrate levels [Spearman correlation coefficient (SCC) = 0.13, P = 0.02] and skeletal muscle index (SCC = 0.084, P = 0.002). Of interest was the finding that two main butyrate‐producing bacterial species were both positively associated with the increased capacity for gut microbial synthesis of butyrate [ Faecalibacterium prausnitzii (SCC = 0.25, P = 6.6 × 10−7) and Butyricimonas virosa (SCC = 0.15, P = 0.001)] and for skeletal muscle index [ F. prausnitzii (SCC = 0.16, P = 6.2 × 10−4) and B. virosa (SCC = 0.17, P = 2.4 × 10−4)]. One‐sample MR results showed a causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (β = 0.04, 95% confidence interval 0.029 to 0.051, P = 0.003). Two‐sample MR results further confirmed the causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (β = 0.06, 95% confidence interval 0 to 0.13, P = 0.06). Conclusions Our results may help the future development of novel intervention approaches for preventing or alleviating loss of SMM.

Context Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown. Objective We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri- and postmenopausal women. Design and Methods We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments. Results Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. Dodecanoic acid treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (eg,10, 100 μM). Conclusions This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD.

Many animal experiments and epidemiological studies have shown that the gut microbiota (GM) plays an important role in the development of obesity, but the specific biological mechanism involved in the pathogenesis of disease remain unknown. We aimed to examine the relationships and functional mechanisms of GM on obesity in peri- and post-menopausal women.We recruited 499 Chinese peri- and post-menopausal women and performed comprehensive analyses of the gut microbiome, targeted metabolomics for short-chain fatty acids in serum, and host whole-genome sequencing by various association analysis methods.Through constrained linear regression analysis, we found that an elevated abundance of Bacteroides fragilis (B. fragilis) was associated with obesity. We also found that serum levels of acetic acid were negatively associated with obesity, and that B. fragilis was negatively associated with serum acetic acid levels by partial Spearman correlation analysis. Mendelian randomization analysis indicated that B. fragilis increases the risk of obesity and may causally down-regulate acetic acid levels.We found the gut with B. fragilis may accelerate obesity, in part, by suppressing acetic acid levels. Therefore, B. fragilis and acetic acid may represent important therapeutic targets for obesity intervention in peri- and post-menopausal women.

ObjectiveEarly monitoring of plasma human chorionic gonadotropin (β-hCG) level is vital in predicting pregnancy outcome. This study investigated the predictive value of serum β-hCG level on the seventh day after frozen–thawed embryo transfer (FET) for ongoing pregnancy (OP) and adverse pregnancy (AP).DesignRetrospective study.SettingThe Reproductive and Genetic Center of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, China.Participants1061 pregnant women who underwent FET between January 2014 and January 2017.Primary and secondary outcome measuresPregnancy outcome.ResultsSerum β-hCG levels on the seventh day after FET were higher in the single OP group compared with the biochemical pregnancy group (pConclusionSerum β-hCG on the seventh day after FET has good clinical significance for the prediction of OP and AP.

Purpose Menopause is a crucial physiological transition during a woman’s life, and it occurs with growing risks of health issues like osteoporosis. To identify postmenopausal osteoporosis-related genes, we performed transcriptome-wide expression analyses for human peripheral blood monocytes (PBMs) using Affymetrix 1.0 ST arrays in 40 Caucasian postmenopausal women with discordant bone mineral density (BMD) levels. Methods We performed multiscale embedded gene coexpression network analysis (MEGENA) to study functionally orchestrating clusters of differentially expressed genes in the form of functional networks. Gene sets net correlations analysis (GSNCA) was applied to assess how the coexpression structure of a predefined gene set differs in high and low BMD groups. Bayesian network (BN) analysis was used to identify important regulation patterns between potential risk genes for osteoporosis. A small interfering ribonucleic acid (siRNA)-based gene silencing in vitro experiment was performed to validate the findings from BN analysis. Result MEGENA showed that the “T cell receptor signaling pathway” and the “osteoclast differentiation pathway” were significantly enriched in the identified compact network, which is significantly correlated with BMD variation. GSNCA revealed that the coexpression structure of the “Signaling by TGF-beta receptor complex pathway” is significantly different between the 2 BMD discordant groups; the hub genes in the postmenopausal low and high BMD group are FURIN and SMAD3 respectively. With siRNA in vitro experiments, we confirmed the regulation relationship of TGFBR2–SMAD7 and TGFBR1–SMURF2. Main Conclusion The present study suggests that biological signals involved in monocyte recruitment, monocyte/macrophage lineage development, osteoclast formation, and osteoclast differentiation might function together in PBMs that contribute to the pathogenesis of postmenopausal osteoporosis.

This study aimed to explore the prognostic role of dipeptidyl peptidase 4 (DPP4) expression in hepatocellular carcinoma (HCC). DPP4 expression was measured in formalin-fixed paraffin-embedded specimens that were gathered from 327 HCC patients. Immunohistochemistry analyses were utilized to examine DPP4 expression characteristics and prognostic values (overall survival (OS) and time to recurrence) of DDP4 in HCC tissues. In addition, a patient-derived xenograft (PDX) model was used to assess the correlation between DPP4 expression and tumor growth in vivo. DPP4 was expressed in low levels in HCC tissues in contrast to paired peritumoral tissues (38 cases were down-regulated in a total of 59 cases, 64.4%. P=0.0202). DPP4 expression was significantly correlated with TNM stage (P=0.038), tumor number (P=0.035), and vascular invasion (P=0.024), and significantly reduced in patients who were in TNM stages II and III-V, with multiple tumors, and with microvascular invasion compared to patients with TNM stage I, single tumor, and no microvascular invasion. Notably, HCC tissues with low expression of DPP4 had poor OS (P=0.016) compared with HCC tissues with high expression of DPP4, and results from PDX model showed that tumor growth was significantly faster in HCC patients that lowly expressed DPP4 compared to those with highly expressed DPP4. Our findings suggested that low levels of DPP4 could impact the aggressiveness of HCC and contribute to a poor prognosis.

Zona pellucida (ZP), which is composed of at most four extracellular glycoproteins (ZP1, ZP2, ZP3, and ZP4) in mammals, shelters the oocytes and is vital in female fertility. Several studies have identified the indispensable roles of ZP1–3 in maintaining normal female fertility. However, the understanding of ZP4 is still very poor because only one study on ZP4-associated infertility performed in rabbits has been reported up to date. Here we investigated the function of mammalian Zp4 by creating a knockout (KO) rat strain (Zp4−/− rat) using CRISPR–Cas9-mediated DNA-editing method. The influence of Zp4 KO on ZP morphology and some pivotal processes of reproduction, including oogenesis, ovulation, fertilization, and pup production, were studied using periodic acid–Schiff’s staining, superovulation, in vitro fertilization, and natural mating. The ZP morphology in Zp4−/− rats was normal, and none of these pivotal processes was affected. This study renewed the knowledge of mammalian Zp4 by suggesting that Zp4 was completely dispensable for female fertility.

To investigate the effects of gestational diabetes mellitus (GDM) on time to delivery and perinatal outcomes in full-term pregnancies underwent dinoprostone-induced labor.GDM patients that underwent labor induction with dinoprostone vaginal inserts were retrospectively recruited. Full-term pregnancies with normal glucose tolerance (NGT) that underwent labor induction at the same period were recruited as control. Time to delivery and perinatal outcomes were compared between the two groups.A total of 1555 pregnancies with 226 GDM and 1329 NGT were recruited. GDM pregnancies had older ages, lower gestational age, higher body mass index (BMI) and abortion history, and more multigravida than NGT pregnancies (P0.05). Univariate analysis showed no significant difference in time to delivery and delivery rates between the two groups. However, after adjusted in a multivariate analysis model, the delivery rates of GDM women delivered within 12, 24, 36 or 48 h and those vaginally delivered within 12 or 36 h were significantly lower than those in the NGT group (P0.05). Perinatal outcomes were clinically similar between the two groups.GDM did not affect the time to delivery, cesarean delivery and other perinatal outcomes in Chinese women underwent dinoprostone-induced labor. However, it may be associated with the lower rates of delivery within different time intervals.

OBJECTIVE: Genome-wide association studies (GWAS) have successfully identified numerous genetic variants associated with diverse complex phenotypes and diseases, and provided tremendous opportunities for further analyses using summary association statistics. Recently, Pickrell et al. developed a robust method for causal inference using independent putative causal SNPs. However, this method may fail to infer the causal relationship between two phenotypes when only a limited number of independent putative causal SNPs identified. Here, we extended Pickrell’s method to make it more applicable for the general situations. METHOD: We extended the causal inference method by replacing the putative causal SNPs with the lead SNPs (the set of the most significant SNPs in each independent locus) and tested the performance of our extended method by using both simulation and empirical data. RESULTS: Simulations suggested that when the same number of genetic variants are used, our extended method had similar distribution of test statistic under the null model as well as comparable power under the causal model compared with the original method by Pickrell et al. But in practice, our extended method would generally be more powerful because the number of independent lead SNPs was often larger than the number of independent putative causal SNPs. And including more SNPs on the other hand would not cause more false positives. By applying our extended method to summary statistics from GWAS for blood metabolites and femoral neck bone mineral density (FN-BMD), we successfully identified 10 blood metabolites that may causally influence FN-BMD. CONCLUSION: We extended a causal inference method for inferring putative causal relationship between two phenotypes using summary statistics from GWAS, and identified a number of potential causal metabolites for FN-BMD, which may provide novel insights into the pathophysiological mechanisms underlying osteoporosis.

Objective This study was performed to replicate the associations of genetic polymorphisms within nuclear factor-κB (NF-κB) signaling pathway genes with rheumatoid arthritis (RA), and to further examine genetic interactions in a Chinese population. Methods A total of eleven single-nucleotide polymorphisms (SNPs) were genotyped in 594 RA patients and 604 healthy controls. Results Genetic association analysis revealed that NFKBIE rs2233434, TNIP1 rs10036748 and BLK rs13277113 were significantly associated with RA, cyclic citrullinated peptide (CCP)-positive RA and rheumatoid factor (RF)-positive RA, and TNFAIP3 rs2230926 was significantly associated with CCP-positive RA. Significant additive interaction was observed between NFKB1 rs28362491 and IKBKE rs12142086 (RERI = 0.76, 95% CI 0.13–1.38; AP = 0.57, 95% CI 0.11–1.03), NFKBIE rs2233434 and BLK rs13277113 (RERI = 1.41, 95% CI 0.88–1.94; AP = 0.85, 95% CI 0.50–1.20), NFKBIL rs2071592 and TNIP1 rs10036748 (RERI = 0.59, 95% CI 0.17–1.02; AP = 0.46, 95% CI 0.05–0.87), UBE2L3 rs5754217 and TNFSF4 rs2205960 (RERI = 0.50, 95% CI 0.16–0.84; AP = 0.57, 95% CI 0.09–1.05). Significant multiplicative interaction was detected between BLK rs13277113 and UBE2L3 rs5754217 (p = 0.02), BLK rs13277113 and TNFSF4 rs2205960 (p = 0.03). Conclusions Our results lent further support to the role of NF-κB signaling pathway in the pathogenesis of RA from a genetic perspective.

Previous studies found that tea consumption was related to a reduction in the risks of some chronic diseases, but limited data are available on bone health. This study aimed to examine the associations of tea consumption with hip bone strength in Chinese women.Cross-sectional study.The participants were from the ongoing Guangzhou Nutrition and Health Study. This was a cohort study started in 2008. The examination data conducted between June 2010 and December 2013 were used.A total of 1,495 Chinese women aged more than 40 years were included.Tea consumption, socio-demographic information and lifestyle habits were collected by a face-to-face questionnaire. Hip bone mineral density (BMD) and geometric parameters, i.e. cross-sectional area (CSA), section modulus (Z) and buckling ratio (BR), were generated by dual-energy X-ray absorptiometry. The associations of tea consumption with bone phenotypes were detected by analysis of covariance and multiple linear regression models after adjusting for age, body mass index, years since menopause, physical activity, dietary-protein intake, dietary-calcium intake, calcium tablet intake, drinking status and smoking status.Tea drinkers (n = 732) had approximately 1.9% higher BMD (p0.05) and 3.6% lower BR (p0.05) than non-tea drinkers (n = 763). The dose-response relationships of BMD, BR or CSA with total tea consumption were identified (p-trend0.05). Tea drinking was found to be a significant and independent predictor of BMD (β = 0.068, p0.05) or BR (β = -0.079, p0.05).Tea consumption was associated with increased bone strength in middle-aged and elderly Chinese women.

Heat stress induces oxidative stress, and reduces antioxidant defenses of birds, which may affect poultry-production performance. Dietary antioxidants may protect against heat stress. We evaluated the effect of increasing concentrations of dietary curcumin on antioxidant parameters of hens under high-temperature conditions for nine weeks. Roman laying hens (n = 336, 22 weeks old, 1420 g weight) were divided into three treatment groups. The first group served as a thermo-neutral control (kept at 25 ± 1 °C). The second group was exposed to high temperatures (32 ± 1 °C, 6 h/day), and fed a basal diet. The third group was further divided into five groups, and all were exposed to high temperatures (32 ± 1 °C, 6 h/day) and provided a basal diet supplemented with 100, 150, 200, 250, 300 mg/kg curcumin (H1, H2, H3, H4, H5). All treatments included four replicates of 12 hens. Total superoxide dismutase (SOD) activity was significantly higher in H2 and H3 groups, and total antioxidant capacity (T-AOC) was higher in H2, H3, and H5 groups. Catalase (CAT) and glutathione peroxidase (GSH-Px) activities were significantly higher in the H3 group. Malondialdehyde concentrations were lower in curcumin supplemented hens compared to control groups hens. Hens in all curcumin treatment groups had slightly (but non-significantly) higher activities of CAT, SOD, GSH-Px, and T-AOC in liver, heart, and lung tissues, compared to heat stressed control group. It is concluded that dietary curcumin given to laying hens under heat stress may enhance their antioxidant status, and ameliorate stressful environmental conditions.

Zona pellucida (ZP), which enwraps the oocyte during folliculogenesis, initially forms in the primary follicle and plays an important role in female fertility. Here, we investigated a mouse strain (“mutant mice” for short) carrying two types of ZP defects in folliculogenesis, i.e., ZP thinned (but intact) and ZP cracked, caused by targeted mutation in the Zp1 gene. Using this mutant mouse strain and wild-type mouse as control, we studied the effects of the ZP defects on the development of oocytes and granulosa cells during folliculogenesis. For each ZP defect, we examined the morphology of transzonal projections and apoptosis of granulosa cells in the corresponding growing follicles, as well as the morphology of corresponding ovulated eggs and their abilities to develop into viable individuals. Our results suggested that ZP integrity rather than thickness or porosity is crucial for preventing the ectopia of granulosa cells, maintaining adequate routine bilateral signaling between oocyte and surrounding granulosa cells, and thus for ensuring the survival of granulosa cells and the establishment of the full developmental competence of oocytes. This is the first study to elucidate the effects of different degrees of ZP defects caused by the same gene mutation, on the apoptosis of granulosa cells and developmental competence of oocytes, and to explore the potential mechanisms underlying these effects.

The liver performs a significant role in innate and adaptive immunity. Heat stress causes oxidative stress in liver tissues and reduces the immune responses of laying hens which can cause several diseases affecting poultry-production performance. Hepatic inflammation is a common trigger of liver disease, which is reflected by hepatic tissue damage leading to fibrogenesis and hepatocellular carcinoma. Dietary manipulation of curcumin has been proposed to ameliorate the immune status of chickens under heat stress. Thus, this study aimed to investigate the effect of curcumin supplementation on TLR4 mediated non-specific immune response in liver of laying hens under high-temperature conditions. Experimental groups contained two controls groups (high temperature and thermo-neutral control (HC and NC) fed basal diet) and three high-temperature curcumin treatments groups (HT100, HT200 and HT300). Laying hens in HC and HT groups exposed 6 h/day heat stress (32 ± 1 °C). The results of present study showed that heat stress curcumin treatment group had reduced inflammatory responses (IL-6, IL-1β, TNF-α) as compared to HC and NC group. Pathological lesions and DNA damage of immune tissues were decreased in heat stress curcumin supplementation as compared to HC and NC group. Furthermore, PCNA, TLR4 and its downstream gene expression as well as protein expression (TLR4, NF-κB and PCNA) were significantly down regulated in heat stress curcumin supplemented group as compared to HC and NC group. Therefore, it is concluded that heat stressed hens supplemented with dietary curcumin enhance the immunity of laying hens and combat stressful environmental conditions.

Background Emerging evidence indicates that some hematological markers have critical value in evaluating treatment response. This study was performed to determine the clinical value of hemoglobin (Hb), platelet (Plt), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ). Methods Fifty-two RA patients receiving TCZ were recruited and followed for 6 months. The values of abovementioned hematological markers were collected. Clinical disease activity index (CDAI) and disease activity score based on 28 joints (DAS28)-ESR were calculated. Correlation analysis was conducted by calculating Pearson's correlation coefficient. The change in disease activity between groups according to the baseline level of hematological markers was compared by t test. Results Significant correlation between change in NLR (△NLR), change in PLR (△PLR), and change in CDAI (△CDAI) was found (△NLR: r = 0.30, P = 0.03; △PLR: r = 0.31, P = 0.03). The change in Plt (△Plt) was correlated with change in DAS28-ESR (△DAS28-ESR) (r = 0.36, P = 8.24 × 10-3 ). Greater improvement in CDAI was seen in patients categorized into Plt high group (t = 2.06, P = 0.04), NLR high group (t = 2.15, P = 0.04), and PLR high group (t = 2.41, P = 0.02) compared with the contrast group. Conclusion Our study demonstrated that △Plt, △NLR, and △PLR could be used to monitor the clinical response to TCZ. RA patients with high baseline levels of Plt, NLR, and PLR achieved more improvement, indicating these hematological markers might be utilized to guide TCZ treatment.

Emerging clinical evidence has implied that alkaline phosphatase (ALP) may contribute to gestational diabetes mellitus (GDM). However, there were no studies to reveal the independent and prospective associations between ALP and GDM. Our aim was to explore the independent and prospective associations between early maternal ALP level and GDM risk and glucose regulation. In a prospective cohort study with 2073 singleton mothers at four maternity units in China, maternal serum ALP levels were measured before 20 gestational weeks. Using logistic regression, we analyzed the relationship between maternal ALP level and risk of GDM. We further explored the relationships of ALP level to fasting blood glucose (FBG), 1-h and 2-h post-load blood glucose (1-h, 2-h PBG) with multiple linear regression. Finally, we analyzed the association between maternal ALP level and isolated impaired fasting glucose (i-IFG) and isolated impaired glucose tolerance (i-IGT) risk. The maximum value of maternal ALP level was 90 U/L, within the normal range. After adjustment for confounding factors, the odds ratio (ORs) of GDM increased linearly with ALP level (p for overall association = 0.002, p for nonlinear association = 0.799), with the OR comparing the highest versus lowest quartile of 2.47 (95% CI 1.47, 4.15). Moreover, each additional of 10 U/L ALP level was associated with a 2% higher FBG (p = 0.043) and a 12% higher 1-h PBG (p = 0.004). Higher ALP level also increased the risk of i-IFG (OR 3.73, 95% CI 1.17–11.86) and i-IGT (OR 2.03, 95% CI 1.07–3.84). Even within the upper limit of normal, higher early maternal ALP level could increase the risk of GDM. Moreover, both FBG and PBG were increased with early maternal ALP.

Bilirubin concentrations have been recently reported to be negatively associated with type 2 diabetes mellitus. We examined the association between bilirubin concentrations and gestational diabetes mellitus. In a prospective cohort study, 2969 pregnant women were recruited prior to 16 weeks of gestation and were followed up until delivery. The value of bilirubin was tested and oral glucose tolerance test was conducted to screen gestational diabetes mellitus. The relationship between serum bilirubin concentration and gestational weeks was studied by two-piecewise linear regression. A subsample of 1135 participants with serum bilirubin test during 16-18 weeks gestation was conducted to research the association between serum bilirubin levels and risk of gestational diabetes mellitus by logistic regression. Gestational diabetes mellitus developed in 8.5 % of the participants (223 of 2969). Two-piecewise linear regression analyses demonstrated that the levels of bilirubin decreased with gestational week up to the turning point 23 and after that point, levels of bilirubin were increased slightly. In multiple logistic regression analysis, the relative risk of developing gestational diabetes mellitus was lower in the highest tertile of direct bilirubin than that in the lowest tertile (RR 0.60; 95 % CI, 0.35-0.89). The results suggested that women with higher serum direct bilirubin levels during the second trimester of pregnancy have lower risk for development of gestational diabetes mellitus.

Various environmental factors affect livestock production but heat stress is a major challenge in the poultry farming. Poultry exposes to high temperature alters blood immunological parameters and liver enzymatic function which in turn, suppress the immunity and disease resistance of chickens. Thus, the purpose of present study was to explore the effect of dietary curcumin supplementation on blood immunological biomarker and liver enzymatic activity of laying hens under heat stress conditions. Experimental groups contained two control groups (normal temperature control (NC) and heat stress control (HC) and 3 heat stress curcumin treatment groups (HT100, HT200 and HT300). Hens in HC group with basal diet and heat stress curcumin treatment groups were exposed 6 h/day heat stress (32 ± 1 °C) from 10:00 a.m. to 16:00 p.m. for 9 week. The results of present study showed that heat stressed curcumin treatment group had improved liver weight, WBC values and immunoglobulin level as compared to untreated HC and NC groups. The available results also indicated that laying hens supplemented with curcumin under high temperature conditions had reduced H/L ratio, serum corticosterone levels, inflammatory cytokines response and liver enzymatic activity (ALT) which enhanced the immunity of laying hens under hot climatic conditions. Therefore, it is concluded that curcumin has ability to combat harsh environmental conditions which can be used as anti-inflammatory and immune booster feed additive in the poultry nutrition.

Maternal dietary patterns and macronutrients intake have been shown to affect the development of gestational diabetes mellitus (GDM), but the findings are inconsistent. We aimed to identify maternal dietary patterns and examine their associations with GDM risk, and to evaluate the contributions of macronutrients intake to these associations. We included 2755 Chinese pregnant women from the Tongji Maternal and Child Health Cohort. Dietary intakes were assessed using a validated semi-quantitative FFQ 2 weeks before the diagnosis of GDM. GDM (n 248) was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test at 24–28 weeks gestation. We derived five different dietary patterns from a principal component analysis. The results showed that high fish–meat–eggs scores, which were positively related to protein intake and inversely related to carbohydrate intake, were associated with a higher risk of GDM (adjusted OR for quartile 4 v. quartile 1: 1·83; 95 % CI 1·21, 2·79; Ptrend=0·007) and higher plasma glucose levels. In contrast, high rice–wheat–fruits scores, which were positively related to carbohydrate intake and inversely related to protein intake, were associated with lower risk of GDM (adjusted OR for quartile 3 v. quartile 1: 0·54; 95 % CI 0·36, 0·83; Ptrend=0·010) and lower plasma glucose levels. In addition, dietary protein and carbohydrate intake significantly contributed to the associations between dietary patterns and GDM risk or glucose levels. These findings suggest that a dietary pattern characterised by high protein and low carbohydrate intake in pregnancy was associated with a higher risk of GDM, which may provide important clues for dietary guidance during pregnancy to prevent GDM.

This study was done to evaluate the effects of Chinese herbal medicine (CHM) and ginger powder on layers-production performance, serum metabolites and antioxidant status under heat stress condition. Two hundred and fifty Lohmann layers were randomly divided into 5 different, including two controls and three experimental groups (H1, H2, and H3). Control groups were fed the basic diet without supplementation, while, the feed of three experimental groups was supplemented with 3.32 g CHM, 10 g ginger powder, and 10 g ginger powder+ 3.32 g CHM per kg of diet, respectively. Results showed that feed consumption and production rate were decreased in the HC group, while, feed intake and production significantly improved when birds were given supplemented diet. The production rate and feed intake of the H3 group were even significantly higher than the NC group. The birds that received supplemented diet had higher glucose level compared to HC. Triglycerides and serum cholesterol had significantly decreased level in supplemented groups compared to HC. Fungal catalase (CAT) level was significantly improved in H2 and H3 groups. Nitric oxide (NO), glutathione peroxidase (GSH-PX) and Total Protein (T-AOC) level were significantly improved in supplemented groups. Findings showed that ginger powder and CHM could be a viable alternative to the synthetic antibiotic in poultry feed.

Body composition and bone strength are closely associated. How lean mass (LM) and fat mass (FM) contribute to bone strength remains ambiguous. We investigated the associations of total body LM and FM with changes in predicted hip bone strength over a period of 3 years in 1,743 postmenopausal Chinese women from the communities of Guangzhou, China. The body compositions of the women were obtained with dual-energy X-ray absorptiometry. We used the hip structure analysis program to obtain the bone parameters at the femoral neck region, including the bone mineral density (BMD), cross-sectional area (CSA), cortical thickness (CT), section modulus (SM) and buckling ratio (BR). We found the FM and LM were positive predictors for hip bone strength (β > 0, P LM > βFM), while the contribution of FM to the BR and its annual percent change was higher than LM (|βFM| > |βLM|). Further analysis found that the associations of FM and LM with bone parameters were stronger in the underweight and normal weight participants (|βBMI1| > |βBMI2|). Overall, FM and LM had positive but differential effects on predicted hip bone strength, with a higher impact in the thinner participants.

Summary Background & aims Oxidative stress has been implicated in the pathogenesis of gestational diabetes mellitus (GDM). Vitamin C as natural antioxidant may help to increase the body's antioxidant capacity. The study is aimed to determine whether vitamin C intake during pregnancy is associated with lower risk of GDM. Methods Women with singleton pregnancy and without any history of diabetes were drawn from the ongoing Tongji Maternal and Child Health Cohort (TMCHC). Oral glucose tolerance tests (OGTT) were conducted during weeks 24–28 of gestation to screen for GDM. A validated food frequency questionnaire (FFQ) was used to assess dietary intake during mid pregnancy. Use of multivitamins and specific supplements of vitamin C was assessed by questionnaires. Odds ratios (ORs) of GDM risk were calculated by logistic regression models, adjusted for potential confounders. Results 344 (11.4%) of the 3009 women were diagnosed with GDM. Dietary vitamin C intake was inversely associated with the risk of GDM. Women with above adequate dietary vitamin C intake (more than 200 mg/day) experienced lower odds of GDM (OR 0.68, 95% CI: 0.49–0.95) than those with adequate intake (115–200 mg/day). There was no association between the total consumption of vitamin C and the risk of GDM (OR 1.04, 95% CI: 0.71–1.53). Conclusion This data suggests that higher dietary consumption of vitamin C during pregnancy is independently associated with lower odds of GDM. Above 200 mg/day of dietary vitamin C intake may help reduce the odds of GDM. However, no such association between total vitamin C intake and the risk of GDM was found. Hence, sufficient vegetables and fruits rich in vitamin C should be recommended to protect pregnant women from developing gestational diabetes.

Background To investigate the effect of different delivery modes and related obstetric factors on the short-term strength of the pelvic floor muscle after delivery in Chinese primipara. Methods A total of 4769 healthy Chinese primiparas at postpartum 6–8 weeks were interviewed. According to the difference of delivery mode, the selected primiparas were divided into 2 groups, including cesarean delivery group containing 2020 and vaginal delivery group containing 2749. All the vaginal deliveries were further divided into 3 groups, including episiotomy group containing 2279, perineal laceration group containing 398, and forceps assisted group containing72. The scales of their pelvic floor muscle (PFM) strengths were examined by specially trained personnel using digital palpation (Modified Oxford scale:0–5 grade). According to participants’ willingness, if the PFM strength was weak (0 or 1 grade), at-home PFM training would be recommended and an electrical stimulation combined with biofeedback therapy would be conducted for them in hospital. Twelve weeks after delivery, the PFM strength would be measured again. For statistical analysis, t-test, one-way variance analysis, Chi-square analysis, Kruskal-Wallis test H, Mann-Whitney U test and Wilcoxon test were carried out. Results The PFM strength in cesarean delivery group was higher than in vaginal delivery group (p 0.05). After accepting PFM training at home and therapy in hospital, 305 women showed increased PFM strength (p

Summary Background & aims Delayed onset of lactogenesis II (OL) negatively affects breastfeeding and consequently, the health of the newborn. Few studies have examined the association between gestational weight gain (GWG) throughout pregnancy and risk of delayed OL. Methods We used data from a prospective cohort study in Wuhan of China, which enrolled pregnant women at 8–16 weeks of gestation and followed-up regularly. GWG was assessed by the last available weight measurement (LAWM) during pregnancy and the self-reported pre-pregnancy weight at enrollment. The outcome was delayed OL self-reported after 4 days postpartum. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from multivariate logistic regression. Results Delayed OL was reported by 18.4% of the 3282 participants. After adjustment for the demographic, clinical and breastfeeding characteristics, compared to the lowest quartile 1 of GWG, ORs (95% CIs) were 1.20 (0.91, 1.57) for quartile 2, 1.47 (1.13, 1.92) for quartile 3, and 1.42 (1.08, 1.86) for quartile 4 (P for trend = 0.006). When GWG was classified by the 2009 Institute of Medicine (IOM) guidelines, compared with women with adequate GWG, the adjusted ORs (95% CIs) were 0.82 (0.61, 1.10) for inadequate GWG, and 1.13 (0.93, 1.38) for excessive GWG. Conclusions Women with higher GWG throughout pregnancy are more likely to suffer from delayed OL in Chinese population.

With the implementation of the "Education and Training Program for Outstanding Agricultural and Forestry Talents" in our country, our university established the "Outstanding Class" for students majoring in the animal science. We also carried out a series of educational management and curriculum reforms to cultivate students' systematic model of thinking and the ability of technology innovation. In this paper, we designed a comprehensive experiment that focused on analyzing early and late feather genetic traits of chicken. The students initially observed the phenotype of chickens and gradually were led into genetics analysis. We introduced the breeding practice, and guided the students to use genetic theories to breed chick strains of early and late feather traits. The experiment is not only based on the sex-linkage theory and sex determination mechanism, but also molecular genetics technologies, such as genomic DNA extraction, amplification, enzyme digestion and electrophoresis. Conducting this experiment can enhance students' comprehensive analysis ability and professional skills, as well as be beneficial to cultivate their scientific research interests and curiosity on animal sciences. Thus, we integrated the genetics theories into animal breeding practice that meet the requirement of comprehensive applied talents of animal science specialty. The teaching ideas and methods described in this paper can be applied to other biological experiment teaching practice.

This study aimed to qualify relevant factors for vaginal delivery among women who underwent labor induction with vaginal dinoprostone (PGE2) insert in a Chinese tertiary maternity hospital.A retrospective study was conducted in Hubei Maternal and Child Health Hospital. A total of 1656 pregnancies that underwent labor induction with vaginal dinoprostone insert between January and August 2016 were finally included in this study. Data were analyzed using univariate and multivariable regression modeling.Of 1656 women with PGE2-induced labor at term, 396 (23.91%) gave birth by cesarean section, 1260 (76.09%) had a vaginal delivery among which 921 (55.61%) delivered vaginally within 24 h. Multivariable regression analysis showed that maternal age (p .001, OR = 0.89, 95%CI 0.85-0.93), parity (multiparous versus nulliparous, p .001, OR = 8.74, 95%CI 4.36-17.50), baseline fetal heart rate (p = .009, OR = 0.98, 95%CI 0.96-0.99), and birth weight (p .001, OR = 0.37, 95%CI 0.28-0.51) were significantly correlated with vaginal delivery. Moreover, body mass index (p .001, OR = 1.11, 95%CI 1.05-1.19), parity (multiparous versus nulliparous, p .001, OR = 6.57, 95%CI 2.37-18.23), baseline fetal heart rate (p = .004, OR = 0.96, 95%CI 0.94-0.99), and birth weight (p .001, OR = 0.34, 95%CI 0.21-0.54) were independent predictors of vaginal delivery within 24-h.Our findings suggested a vaginal delivery rate of 76.09% when dinoprostone vaginal insert was used for labor induction, which was markedly higher than the overall annual vaginal delivery rate of 65.1% in China during 2014. Maternal age, parity, baseline fetal heart rate, and birth weight were significant factors for vaginal delivery. This study enables us to better understand the efficiency of dinoprostone and the potential predictors of vaginal delivery in dinoprostone-induced labor, which may be helpful to guide the clinical use of dinoprostone and therefore provide better service clinically.

Objectives To investigate the effectiveness of a 6-month Liuzijue qigong (LQG) program in promoting physical and psychosocial function in individuals with chronic obstructive pulmonary disease (COPD). Design Single-blind, randomized controlled trial. Setting Seven hospital respiratory care centers in Beijing. Participants Individuals with COPD (N = 126; mean age 71.1 ± 2.7, range 65–85). Methods Participants were randomly assigned to one of two groups: LQG (n = 63) and control (n = 63). Subjects in the LQG group received a LQG program consisting of four 45-minute sessions each week and daily walking for 30 minutes for 6 months. Control subjects walked daily for 30 minutes. Data collection was performed at baseline, at 6 weeks, and at 6 months. Primary outcomes involved functional capacity, and secondary outcomes involved quality of life. Results The LQG group had greater improvements in the 6-minute walk test (P = .02); specific airway conductance (P = .02); monitored functional task evaluation (P = .04); Medical Outcomes Study 36-item Short-Form Health Survey (SF-36; general health (P

Objectives To examine the relationship between poor sleep quality during pregnancy and the risk of gestational diabetes mellitus (GDM). Methods A total of 4066 singleton pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC) without overt diabetes before pregnancy were analyzed. Sleep quality and duration during early pregnancy were self-reported by enrolled women at their first antenatal care visit before 16 weeks of gestation. Gestational diabetes mellitus (GDM) was assessed with a 75-g, 2-h oral glucose tolerance test at 24–28 weeks of gestation. Information about self-reported sleep quality and duration in mid-pregnancy were also collected at this time. Odds ratios (OR) and 95% CIs were calculated by multivariable logistic regression models, and adjusted for potential confounders to estimate the effect of poor sleep quality and the interaction between sleep quality and duration on the development of GDM. Stratified analyses were performed according to age, parity, family history of diabetes and napping. Results A total of 335 (8.2%) participants were diagnosed with GDM. Poor sleep quality was reported in 259 (6.4%) women during early pregnancy and 248 (6.1%) in mid-pregnancy. The risk of GDM was increased in women with poor sleep quality during early pregnancy (OR 1.77, 95% CI 1.20–2.61). No association was found between poor sleep quality during mid-pregnancy and the risk of GDM. The risk of GDM was highest in women with poor sleep and longer nighttime sleep duration during early pregnancy (OR 2.27, 95% CI 1.20–4.29) when compared with those who reported good sleep and 7.0–8.5 h of sleep duration per night. Stratified analysis found that the association between poor sleep quality in early pregnancy and the risk of GDM was stronger among women aged ≥30 years (OR 2.35, 95% CI 1.35–4.09) and those with a family history of diabetes (OR 4.02, 95% CI 1.54–10.48). Conclusions Poor sleep quality during early pregnancy was associated with an increased risk of GDM. Screening for and treating sleep problems in early pregnancy could potentially reduce the risk of GDM.

To compare perinatal outcomes of dinoprostone for induced labor in pregnancies with a borderline versus normal amniotic fluid index (AFI) at term, and to investigate the related factors affecting outcomes of cesarean section.The retrospective study was carried out in Hubei Maternal and Child Health Hospital with singleton pregnancies of 37-42 weeks' gestation from January to August 2016. A total of 992 subjects were divided into two groups: borderline AFI group (n =125) with 5 AFI ≤ 8 and normal AFI group (n = 867) with 8 AFI ≤ 24.Time to delivery (P =0.004) and use of oxytocin augmentation (P = 0.011) were significantly lower in pregnancies with borderline AFI. There were no significant differences between the two groups in terms of delivery mode, time to onset of labor, fetal distress, Apgar scores, meconium-stained amniotic fluid, birth weight, or incidences of admission to neonatal intensive care unit (NICU). Gestational hypertension and birth weight were the major factors affecting outcomes of cesarean section in the borderline group (odds ratio [OR] = 13.61, 95% confidence interval [CI] 1.96-94.49, P =0.008 and OR = 1.003, 95% CI 1.001-1.005, P =0.001, respectively). Maternal age (OR = 1.12, 95% CI 1.06-1.19, P 0.001), parity (OR = 7.57, 95% CI 3.05-18.76, P 0.001), biparietal diameter (OR = 0.55, 95% CI 0.33-0.91, P = 0.021), and meconium-stained amniotic fluid (OR = 1.56, 95% CI 1.12-2.17, P = 0.009) were related factors in the normal group.The perinatal outcomes of dinoprostone for induced labor are comparable between the two groups. Gestational hypertension and birth weight are factors related to outcomes of cesarean section in the borderline group.

Summary Background & aims Gestational diabetes mellitus is associated with adverse short- and long-term consequences for both the mother and the offspring. To examine the relationship between the rates of gestational weight gain (RGWG) during early and mid-pregnancy and the risk of gestational diabetes mellitus (GDM). Methods 2090 singleton pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC) without overt diabetes before pregnancy were analyzed in our study. Gestational weight were measured regularly in every antenatal visit. Gestational diabetes mellitus was assessed with the 75-g, 2-h oral glucose tolerance test at 24–28 weeks of gestation. Multivariable logistic regression was performed to estimate effect of RGWG on GDM. Results A total of 8.3% (n = 173) of pregnant women were diagnosed with GDM. Women with elevated rate of gestational weight gain prior to glucose screening test (RGWG-PG) increased the risk of GDM (adjusted p -trend = 0.004; odds ratios (OR) 1.64, 95% confidence intervals (CI) 1.01–2.68 and OR 2.30,95% CI 1.44–3.66 for 0.297–0.384 kg/wk and 0.385 kg/wk or more vs. 0.213 kg/wk or less, respectively). Women with greater rate of gestational weight gain in the first trimester (RGWG-F) increased the risk of GDM (adjusted p -trend = 0.048; OR 1.83, 95% CI 1.14–2.94 and OR 1.76, 95% CI 1.10–2.83 for 0.086–0.200 kg/wk and 0.201 kg/wk or more vs. −0.025 kg/wk or less, respectively). The rate of gestational weight gain in the second trimester (RGWG-S) was significantly associated with GDM only among women with RGWG-F more than 0.086 kg/wk (adjusted p -trend = 0.035; OR 2.04, 95% CI 1.16–3.59 for 0.658 kg/wk or more vs. 0.418 kg/wk or less). Conclusions Greater early pregnancy weight gain are associated with increased risk of GDM. Elevated weight gain in mid-pregnancy increased the risk of GDM only among pregnant women with greater weight gain in the first trimester.

The human zona pellucida is composed of four glycoproteins (ZP1, ZP2, ZP3, and ZP4) and has an important role in reproduction. Here we describe a form of infertility with an autosomal recessive mode of inheritance, characterized by abnormal eggs that lack a zona pellucida. We identified a homozygous frameshift mutation in ZP1 in six family members. In vitro studies showed that defective ZP1 proteins and normal ZP3 proteins colocalized throughout the cells and were not expressed at the cell surface, suggesting that the aberrant ZP1 results in the sequestration of ZP3 in the cytoplasm, thereby preventing the formation of the zona pellucida around the oocyte.

Context: Fifty-six genomic loci recently were identified as associated with bone mineral density (BMD) in a large meta-analysis study of mainly European-descent subjects. Circulating factors related to calcium and phosphate metabolism, eg, serum levels of calcium, phosphate, vitamin D metabolites, PTH, and alkaline phosphatase (ALP), may affect bone turnover and metabolism. Objective and Design: We aimed to investigate the effects of these reported variants, as well as their interactions with 5 studied circulating factors, on BMD in a southern Chinese prospective cohort (n = 2670). The identified interactions were further replicated in an independent cohort of 800 Chinese females. Results: Approximately half (n = 27) of the reported variants were successfully replicated in our sample of southern Chinese individuals. We further demonstrated a significant interaction between MARK3 and serum ALP levels (Pmeta = 9.89 ×10−6); the effect of MARK3 rs11623869 on BMD was stronger in the presence of high serum levels of ALP. In addition, several interactions between other genes and circulating factors were suggested. Conclusions: Our study has provided an independent replication of associations between several reported loci and BMD in a large sample of southern Chinese individuals. These replicated loci may represent osteoporosis susceptibility genes in both Chinese and European-descent populations. Furthermore, we have shown that serum ALP levels modified the association of MARK3 with BMD. Understanding the mechanisms of the interactions between BMD-related loci and circulating factors may help to determine the pathogenesis of susceptibility to osteoporosis and could have implications for clinical care.