Identification of essential proteins based on edge features and the fusion of multiple-source biological information.

BACKGROUND: A major current focus in the analysis of protein-protein interaction (PPI) data is how to identify essential proteins. As massive PPI data are available, this warrants the design of efficient computing methods for identifying essential proteins. Previous studies have achieved considerable performance. However, as a consequence of the features of high noise and structural complexity in PPIs, it is still a challenge to further upgrade the performance of the identification methods. METHODS: This paper proposes an identification method, named CTF, which identifies essential proteins based on edge features including h-quasi-cliques and uv-triangle graphs and the fusion of multiple-source information. We first design an edge-weight function, named EWCT, for computing the topological scores of proteins based on quasi-cliques and triangle graphs. Then, we generate an edge-weighted PPI network using EWCT and dynamic PPI data. Finally, we compute the essentiality of proteins by the fusion of topological scores and three scores of biological information. RESULTS: We evaluated the performance of the CTF method by comparison with 16 other methods, such as MON, PeC, TEGS, and LBCC, the experiment results on three datasets of Saccharomyces cerevisiae show that CTF outperforms the state-of-the-art methods. Moreover, our method indicates that the fusion of other biological information is beneficial to improve the accuracy of identification.

Sociodemographic features associated with the MoCA, SPPB, and GDS scores in a community-dwelling elderly population.

BACKGROUND: An accurate evaluation of cognitive function, physical health, and psychological health is fundamental for assessing health problems in the elderly population, and it is important to identify the necessity of early therapeutic intervention. The objective of this study was to evaluate the states of mental and physical functions and to investigate the relationships between sociodemographic features and these functions in a community-dwelling elderly population. METHODS: This community-based cross-sectional study was conducted in a suburban district of Shanghai, China. A total of 1025 participants aged 60-89 years underwent investigations of demographic and lifestyle features and a multidimensional geriatric evaluation comprising the Montreal Cognitive Assessment (MoCA), Short Physical Performance Battery (SPPB), and Geriatric Depression Scale (GDS). RESULTS: The results of the multivariate linear regression models demonstrated that the MoCA and SPPB scores decreased with advancing age (all P < 0.01). However, the GDS score did not exhibit an age-related decrease (P = 0.09). Both sex and living alone influenced the MoCA score (P < 0.01 and P = 0.04, respectively), SPPB score (P < 0.01 and P = 0.04, respectively), and GDS score (P < 0.01 and P < 0.01, respectively). A higher education level was related to better MoCA and SPPB scores (all P < 0.01). Furthermore, age and sex had interactive effects on the MoCA score (P = 0.03) and SPPB score (P < 0.01). The kernel-weighted local polynomial smoothing curves exhibited similar trends. CONCLUSIONS: It is imperative to develop a more sensitive evaluation of physical function, and to encourage various intellectually and emotionally stimulating social activity strategies to promote healthy aging, especially in elderly women and those living alone who have a low education level.

Investigating continuation of folic acid supplementation during peri-conceptional period: a community-based cross-sectional study.

BACKGROUND: Maternal folate may not reach an optimal level to prevent neural tube defects if supplementation commenced post-conception or took place pre-conception only. Our study aimed to investigate the continuation of folic acid (FA) supplementation from pre-conception to post-conception during peri-conceptional period and to examine its differences in FA supplementation between the subgroups taking the initiation timing into consideration. METHODS: This study was conducted in two community health service centers in Jing-an District of Shanghai. Women accompanying their children to pediatric health clinics of the centers were recruited and asked to recall information concerning their socioeconomic and previous obstetric characteristics, utilization of healthcare and FA supplementation before and/or during pregnancy. The continuation of FA supplementation during peri-conceptional period were categorized into three subgroups: Supplementing with FA pre- and post-conception; supplementing with FA preconception only or post-conception only; no FA supplements pre-conception and post-conception. The relationship between FA continuation and couples' characteristics were examined as setting the first subgroup as the base reference. RESULTS: Three hundred and ninety-six women were recruited. Over 40% of the women started FA supplementation after conception and 30.3% of them supplemented with FA from pre-conception to the first trimester of their pregnancy. Compared to this one-third of participants, women who didn't supplemented with any FA during peri-conceptional period were more likely to have no utilization of pre-conception healthcare ([Formula: see text]= 2.47, 95% [Formula: see text]: 1.33-4.61) or antenatal care ([Formula: see text]= 4.05, 95% [Formula: see text]: 1.76-9.34), or who had a lower family socioeconomic status ([Formula: see text]= 4.36, 95% [Formula: see text]: 1.79-10.64). Women who supplemented with FA pre-conception only or post-conception only were more likely to have no utilization of pre-conception healthcare ([Formula: see text]= 2.94, 95% [Formula: see text]: 1.79-4.82), or to have no previous pregnancy complication ([Formula: see text]=1.80, 95% [Formula: see text]: 0.99-3.28). CONCLUSION: Over two-fifth of the women started FA supplementation and only one-third of them had an optimal supplementation from pre-conception to the first trimester. Maternal utilization of healthcare before or during pregnancy together with maternal and paternal socioeconomic status may play a role in the continuation to FA supplementation pre- and post-conception.

Preconception thyroid-stimulating hormone levels and adverse pregnancy outcomes.

OBJECTIVE: Evidence for the association between subclinical thyroid dysfunction before conception and its pregnancy outcomes is inconsistent. Thus, we evaluated the relationship between preconception thyroid-stimulating hormone (TSH) levels and adverse pregnancy outcomes. DESIGN: Retrospective cohort study. METHODS: A total of 50,217 women without prior thyroid disease who became pregnant within 1 year after undertaking a routine TSH test in the Chongqing Municipality of China (2010-2016) were studied. Restricted cubic spline regression and logistic regression were used to estimate the association between preconception TSH levels and pregnancy outcomes. The main outcomes were individual and composite adverse pregnancy outcomes (CAPOs) comprising pregnancy loss, small for gestational age, large for gestational age, and preterm birth. RESULTS: Incidence of CAPO was 24.19%. Increased preconception TSH level was positively associated with CAPO (odds ratio [OR]/SD: 1.04, 95% confidence interval [CI]: 1.01-1.07) when TSH was ≥2.1 mIU/L, positively associated with pregnancy loss (OR/SD: 1.06, 95% CI: 1.01-1.12) when TSH was <2.1 mIU/L, negatively and positively associated with preterm delivery when TSH levels were <1.3 mIU/L (OR/SD: 0.90, 95% CI: 0.83-0.97) and >3.0 mIU/L (OR/SD: 1.08, 95% CI: 1.00-1.17), respectively. Women with subclinical hypothyroidism before conception were at a higher risk for CAPO (adjusted odds ratio [aOR]: 1.12, 95% CI: 1.04-1.22), while those with subclinical hyperthyroidism had a higher risk of preterm delivery (aOR: 1.31, 95% CI: 1.01-1.70). CONCLUSIONS: Nonlinear associations were indicated between preconception TSH levels and pregnancy outcomes. Subclinical thyroid dysfunction before conception was associated with an increased risk of adverse pregnancy outcomes.

Preconception reproductive tract infections status and adverse pregnancy outcomes: a population-based retrospective cohort study.

BACKGROUND: Reproductive tract infections can cause serious adverse outcomes for pregnant women such as spontaneous abortion and preterm birth. However, it is unclear whether maternal reproductive tract infection before pregnancy would also be related to any adverse pregnancy outcomes. This study aims to investigate the association of maternal preconception reproductive tract infections with subsequent adverse pregnancy outcomes. METHODS: A retrospective cohort study was conducted in the Chongqing Municipality of China between April 2010 and December 2016. A total of 57,586 women (57,708 pregnancies) from all 39 counties of Chongqing who participated in the National Free Preconception Health Examination Project were included. They all took preconception examinations for gonorrhea, chlamydia, trichomoniasis, syphilis, bacterial vaginosis and candidiasis before pregnancy within one year. Primary outcomes included spontaneous abortion (< 28 weeks gestation), preterm birth (< 37 weeks gestation), macrosomia and low birthweight. RESULTS: Of the 57,708 pregnancies, 2438 (4.22%) had at least one type of reproductive tract infections. Compared with women who were not infected with any reproductive tract infection before pregnancy, women with reproductive tract infections had a higher rate of spontaneous abortion (7.88% vs. 5.62%, p < 0.001). After analyzing by each infection, there were few significant associations between pre-pregnancy infections and adverse outcomes. Preconception syphilis infection was significantly associated with increased odds of spontaneous abortion (aOR = 2.07, 95%CI 1.50-2.85), induced abortion/labour due to medical reasons (aOR = 1.60, 95%CI 1.01-2.54) and preterm birth (aOR = 1.60, 95%CI 1.12-2.30) after adjusting for potential confounders. Preconception trichomoniasis was intended to relate to a higher risk of spontaneous abortion (aOR = 1.65, 95%CI 1.01-2.71), but its impact seemed to be attributed to its co-infection with other RTIs. Women who were chlamydia or bacterial vaginosis positive before pregnancy showed higher odds of macrosomia (aOR = 2.00, 95% CI 1.07-3.74 for chlamydia; aOR = 1.58, 95% CI 1.06-2.34 for bacterial vaginosis). Preconception bacterial vaginosis might also be associated with higher risks of very preterm birth (aOR = 2.16, 95%CI 1.23-3.78) and large for gestational age (aOR = 1.36, 95%CI 1.02-1.81). CONCLUSIONS: Women with infections of the genital tract before pregnancy might also have increased risks of subsequent adverse outcomes including spontaneous abortion, preterm birth and macrosomia.

Clinical observation of posterior scleral reinforcement in the treatment of progressive high myopia in Chinese children: a retrospective study.

OBJECTIVE: To observe the efficacy and safety of posterior sclera reinforcement over time. METHODS: This retrospective single-arm cohort study included children with high myopia who underwent the modified Snyder-Thompson type posterior sclera reinforcement surgery from 03/2015 to 08/2018 at Fuzhou Children's Hospital of Fujian Medical University. Axial length (AL), corneal radius of curvature (CRC), AL/CRC, refractive error, and best-corrected visual acuity (BCVA) were observed from 1 year before the operation to 2 years after. RESULTS: Nineteen children (33 eyes) with high myopia were included. The patients were 4.9 ± 2.7 (range, 2-10) years of age (three patients were 10 years old, all others were ≤ 7 years old). AL increased from 1 year before surgery to 2 years after surgery (from 25.31 ± 1.59 to 26.76 ± 1.52, P < 0.001). The refractive error was smaller 1 year before surgery than at the other timepoints (all P < 0.05). BCVA improved over time (P < 0.001). Changes over time were also observed in horizontal CRC (hCRC), AL/hCRC, AL/vertical CRC (vCRC), and AL/CRC (all P < 0.001), but not in vCRC (P = 0.304). The increase of AL at 2 years after surgery was smaller than at 1 year before surgery and 1 year after surgery (both P < 0.001). The increase of AL/CRC at 2 years after surgery was smaller than at 1 year before surgery (0.04 ± 0.04 vs. 0.07 ± 0.04; P = 0.008). CONCLUSION: In the short term, posterior scleral reinforcement surgery can delay the increase of AL of progressive high myopia.

Prevalence of reproductive tract infections among women preparing to conceive in Chongqing, China: trends and risk factors.

BACKGROUND: Reproductive tract infection has become a major public health issue all over the world for its high and growing prevalence. It can cause adverse pregnancy outcomes in pregnant women and their foetuses. This study aimed to investigate the trends and risk factors of the prevalence of reproductive tract infections among women who prepared to conceive in the Chongqing Municipality (China) from 2012 to 2016. METHODS: A multi-center cross-sectional study was conducted between January 2012 and December 2016. Women aged 20-49 years who intended to get pregnant were recruited for this study. All participants underwent preconception examination, which included testing for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, syphilis, bacterial vaginosis and candidiasis according to the national diagnostic standard. A total of 439,372 women with testing results for all six types of reproductive tract infections were included in our final analyses. Logistic regression and factor analysis were used to determine the possible sociodemographic factors associated with prevalence trends. RESULTS: In our study, the overall positive rate of RTIs among the 439,372 women of reproductive age was 5.03%. Candidiasis was the most common infection in our population (2.47%), followed by bacterial vaginosis (1.28%), syphilis (0.73%), T. vaginalis (0.49%), C. trachomatis (0.20%) and N. gonorrhoeae (0.06%). The prevalence of reproductive tract infections was highest among women aged 35 years and above, with a primary or lower education level, history of pregnancy, delivery, induced abortion, or spontaneous abortion. From 2012 to 2016, the trend of the overall prevalence of reproductive tract infections was V-shaped, decreasing steadily from 2012 to 2015, with a slight rise in 2016. Our results suggest that the distribution change of age, education level, gravidity, parity, and history of induced abortion influenced this trend. CONCLUSION: Since the number of high-risk women who intend to become pregnant is growing in the Chongqing Municipality, pre-conception positive preventions including health education, regular screening, and timely treatment of reproductive tract infections are needed to prevent the impact of reproductive tract infections on maternal health and infant safety.

Reproductive tract infections (RTIs) can cause serious health problems, such as spontaneous abortion and congenital diseases in pregnant women and their foetuses. However, there is a lack of studies focusing on the prevalence of RTIs and their trends among women who intend to conceive. This cross-sectional study examined data collected from 439,372 women during their preconception care to investigate the trend and related risk factors of the prevalence of RTIs, thereby providing essential data for their prevention. Participants were women from all 39 counties in the Chongqing Municipality of China, and data were collected between 2012 and 2016. We found that the overall prevalence of the six types of RTIs among these women was 5.03%, which was relatively lower than that in other populations in previous studies. Age, education level, history of pregnancy or delivery, and history of abortion were all associated with the prevalence of RTIs. The prevalence trend from 2012 to 2016 was V-shaped decreased steadily from 2012 until 2015 and rose slightly in 2016. Our data suggested that this trend might be influenced by changes in the proportion of 'high-risk' women, that is, women with higher age, lower education level, and a history of pregnancy or induced abortion. This study suggests that health education and regular screening are necessary to face new challenges experienced by older women or women with previous pregnancies who intended to get pregnant in recent years in China.

Associations of MCM8 rs3761873 and rs16991617 variants with abnormal uterine bleeding induced by copper intrauterine device.

AIM: Intrauterine device (IUD) is a commonly used contraceptive method worldwide. Abnormal uterine bleeding (AUB) is one of the most common side effects of Cu-IUDs. Since AUB varies among Cu-IUD users, changes in the bleeding-related genetic factors may contribute to AUB. This study aimed to determine the genetic risk factors of AUB after Cu-IUD insertion. METHODS: We conducted a case-control study on women who experienced AUB after Cu-IUD insertion (case:control = 62:59). Six candidate variants were genotyped using the Sequenom MassARRAY. Genotype and allele frequencies were analyzed using SHEsisPlus. We performed Pearson's Chi-squared test to analyze categorical data, and ESEfinder to predict the impact on splicing regulation. RESULTS: MCM8 coding sequence variants: rs3761873-A>C was in Exon 7 and rs16991617 A>G was in Exon 12 of all 19 exons, both of which were significantly different between cases and controls (pallele  = 0.039 and pgenotype  = 0.092). rs6022 and rs6029 in F5 gene and rs3761873 and rs16991617 in the MCM8 gene showed strong linkage disequilibrium (R2 > 0.8). ESEfinder indicated that the variants of MCM8 may affect the splicing regulation. CONCLUSIONS: MCM8 rs376187 and rs16991617 were associated with AUB in Cu-IUDs users. MCM8 may play a role in AUB by regulating functions of reproductive organs and primary ovarian insufficiency. Our findings may improve the understanding of the genetic basis of AUB caused by Cu-IUDs.

miR-3074-5p/CLN8 pathway regulates decidualization in recurrent miscarriage.

Decidualization is essential for the successful establishment of pregnancy, and the dysregulated decidualization may lead to early pregnancy loss. It was previously reported by us that miR-3074-5p could promote apoptosis but inhibit invasion of human extravillous trophoblast (EVT) cells in vitro, and the expression level of miR-3074-5p in villus tissues of recurrent miscarriage (RM) patients was significantly increased. The aim of this study was to preliminarily explore the role of miR-3074-5p played in the decidualization of human endometrial stromal cells (ESCs). It was found that the decidual expression level of miR-3074-5p in RM patients was remarkably higher than that in the control group. The overexpression of miR-3074-5p in the immortalized human ESC line, T-HESCs, showed suppressive effects not only on the cell proliferation, as well as the intracellular expression levels of cyclin B1 (CCNB1), CCND1 and CCNE1 but also on the in vitro-induced decidualization. CLN8 mRNA, encoding an endoplasmic reticulum (ER)-associated membrane protein, was validated to be directly targeted by miR-3074-5p. And, the expression level of CLN8 was continuously increased along with the decidualization process, whereas down-regulated CLN8 expression could inhibit the decidualization of T-HESCs in vitro. Furthermore, contrary to the increased expression level of miR-3074-5p, a significantly decreased CLN8 expression was observed in decidual tissues of RM patients. Collectively, these data suggested that an increased miR-3074-5p expression in ESCs might cause early pregnancy failure by disturbing decidualization of ESCs via the miR-3074-5p/CLN8 pathway, providing a potential diagnostic and therapeutic target for RM.

Co-occurrence subgroups of child sexual abuse, health risk behaviors and their associations among secondary school students in China.

BACKGROUND: Little is known on the co-occurrence and heterogeneity of child sexual abuse (CSA) or health risk behavior (HRB) prevalence nor the associations among the victims. OBJECTIVES: To detect the prevalence and subgroups of adolescents reporting CSAs or HRBs, and to examine the association between the subgroups. METHODS: Participants were secondary school students in a national survey in China (N = 8746). Self-reported CSA and HRB experiences were collected through a computer assisted questionnaire. Prevalence and confidence intervals were calculated. Multigroup latent class analysis (LCA) was used to examine latent subgroups of CSA and HRB. Dual latent class regression analysis was used to examine the association between CSA and HRB classes. RESULTS: A total of 8746 students participated in our study. The prevalence of having ever experienced any of the reported seven CSA items was 12.9%. The preferred LCA model consisted of a three-class CSA latent variable, i.e. "Low CSAs"(95.7% of the total respondents), "Verbal or exhibitionism CSAs"(3.3%), and "high multiple CSAs" (1.1%); and a three-class HRB latent variable, i.e. "Low HRBs"(70.5%), "externalizing HRBs" (20.7%), and "internalizing HRBs" (8.7%). Students in the "Verbal or exhibitionism CSAs" or "high multiple CSAs" classes had higher probabilities of being in "externalizing HRBs" or "internalizing HRBs" classes. The probabilities were higher in "high multiple CSAs" class(male externalizing OR 4.05, 95%CI 1.71-9.57; internalizing OR 11.77, 95%CI 4.76-29.13; female externalizing OR 4.97, 95%CI 1.99-12.44; internalizing OR 9.87, 95%CI 3.71-26.25) than those in "Verbal or exhibitionism CSA"(male externalizing OR 2.51, 95%CI 1.50-4.20; internalizing OR 3.08, 95%CI 1.48-6.40; female externalizing OR 2.53, 95%CI 1.63-3.95; internalizing OR 6.05, 95%CI 3.73-9.80). CONCLUSIONS: Prevalence of CSA items varies. Non-contact CSAs are the most common forms of child sexual abuse among Chinese school students. There are different latent class co-occurrence patterns of CSA items or HRB items among the respondents. CSA experiences are in association with HRB experiences and the associations between latent classes are dose-responded. Multi-victimization has more significantly negative effects. The results could help identify high-risk subgroups and promote more nuanced interventions addressing adverse experiences and risk behaviors among at-risk adolescents.

Neuroprotective Effect of Brimonidine against Facial Nerve Crush Injury in Rats via Suppressing GFAP/PAF Activation and Neuroinflammation.

OBJECTIVE: This study aimed to investigate the potential neuroprotective action of brimonidine against facial nerve crush injury in rats and the possible underlying mechanisms. METHODS: Sixty Wistar adult rats were randomly and equally divided into 3 groups: 40 rats underwent unilateral facial nerve crush injury and were administered with either saline (intraperitoneal, n = 20) or brimonidine 1 mg/kg/day (intraperitoneal, n = 20) for 5 consecutive days. Functional and electromyographic recovery was recorded postoperatively. The facial nucleus of 5 mice in each group was analyzed for mRNA expression levels of GFAP, PAF, NT-4, P75NTR, NF-κB, TNF-α, IL-6, and α2-ARs by qRT-PCR. RESULTS: Brimonidine promoted the recovery of vibrissae movement, eyelid closure, and electrophysiological function in a rat model of nerve crush injury. Hematoxylin and eosin staining and electron microscopy showed significant recovery of Schwann cells and axons in the brimonidine group. Brimonidine attenuated the crush-induced upregulation in GFAP and PAF mRNA (p < 0.05), as well as enhanced the mRNA levels of NT-4 and P75NTR (p < 0.05), while decreased the expression of NF-κB, TNF-α and IL-6 (p < 0.05). CONCLUSIONS: Brimonidine could promote the recovery of facial nerve crush injury in rats via suppressing of GFAP/PAF activation and neuroinflammation and increasing neurotrophic factors. Brimonidine may be apromising candidate agent for the treatment of facial nerve injury.

Complete chloroplast genomes of four Physalis species (Solanaceae): lights into genome structure, comparative analysis, and phylogenetic relationships.

BACKGROUND: Physalis L. is a genus of herbaceous plants of the family Solanaceae, which has important medicinal, edible, and ornamental values. The morphological characteristics of Physalis species are similar, and it is difficult to rapidly and accurately distinguish them based only on morphological characteristics. At present, the species classification and phylogeny of Physalis are still controversial. In this study, the complete chloroplast (cp) genomes of four Physalis species (Physalis angulata, P. alkekengi var. franchetii, P. minima and P. pubescens) were sequenced, and the first comprehensive cp genome analysis of Physalis was performed, which included the previously published cp genome sequence of Physalis peruviana. RESULTS: The Physalis cp genomes exhibited typical quadripartite and circular structures, and were relatively conserved in their structure and gene synteny. However, the Physalis cp genomes showed obvious variations at four regional boundaries, especially those of the inverted repeat and the large single-copy regions. The cp genomes' lengths ranged from 156,578 bp to 157,007 bp. A total of 114 different genes, 80 protein-coding genes, 30 tRNA genes, and 4 rRNA genes, were observed in four new sequenced Physalis cp genomes. Differences in repeat sequences and simple sequence repeats were detected among the Physalis cp genomes. Phylogenetic relationships among 36 species of 11 genera of Solanaceae based on their cp genomes placed Physalis in the middle and upper part of the phylogenetic tree, with a monophyletic evolution having a 100% bootstrap value. CONCLUSION: Our results enrich the data on the cp genomes of the genus Physalis. The availability of these cp genomes will provide abundant information for further species identification, increase the taxonomic and phylogenetic resolution of Physalis, and assist in the investigation and utilization of Physalis plants.

Examining the Effect of Fish Oil Supplementation in Chinese Pregnant Women on Gestation Duration and Risk of Preterm Delivery.

BACKGROUND: Intervention studies have shown that long-chain (LC) n-3 PUFA intake can prolong gestation but the dose-time-effect relations remain unresolved. OBJECTIVES: We examined the effect on gestation duration of 2 doses of supplemental LC n-3 PUFAs. METHODS: We undertook a 3-group parallel randomized controlled trial in areas of China with low (median: 2.1 g/d) and higher (14.3 g/d) fish intake. Unselected women (median: age, 26.2 y; BMI, 20. kg/m2) were randomly assigned at midgestation to take four 0.72-g identical gelatin capsules per day until the last day of the preterm period (<259 days of gestation), when they were asked to stop. Capsules contained fish oil [high fish oil (HFO) group (60% w/w LC n-3 PUFAs)], a 1:3 mixture of fish oil to olive oil [low fish oil (LFO) group (20%)], or olive oil [control (CON) group (0%)], providing 2.0, 0.5, and 0 g/d of LC n-3 PUFAs, respectively. Habitual fish intake was recorded at baseline. Hazard rate ratios (HRRs) for spontaneous delivery <259 days of gestation and <273 days of gestation across groups were estimated by Cox regression. RESULTS: Among 5531 women randomly assigned, 92.5% were included in analyses (1706/1825, 1695/1851, and 1717/1855, respectively). The groups were similar with respect to hazard rates <259 days of gestation [HRR: 1.04 (95% CI: 0.70, 1.53) for LFO compared with CON and 0.90 (95% CI: 0.60, 1.35) for HFO compared with CON], hazard rates <273 days of gestation [HRR: 1.00 (95% CI: 0.86, 1.18) and 0.91 (95% CI: 0.77, 1.07), respectively], and mean gestation durations [differences: 0.2 d (95% CI: -0.5, 0.8) and 0.6 d (95% CI: -0.06, 1.2), respectively]. Inspection of pregnancy survival curves suggested that LC n-3 PUFAs delayed delivery in low fish consumers by 5-10 d and that this effect ceased rapidly after stopping taking the capsules. CONCLUSION: This trial could not substantiate that fish oil prevents preterm birth in Chinese women, possibly because statistical power was too low. This trial was registered at clinicaltrials.gov as NCT02770456.

Puberty timing associated with obesity and central obesity in Chinese Han girls.

BACKGROUND: There is growing scientific evidence supports a link between increased childhood adiposity and early onset of puberty in girls worldwide in recent decades. However, the data from Chinese girls remain ambiguous. The aims of this study were to estimate the puberty milestones and examine attainment of puberty associated with obesity and central obesity in Chinese Han schoolgirls. METHODS: The cross-sectional school-based study examined 2996 Han schoolgirls aged 9 to 19 years from 6 provinces in China. Trained clinicians assessed  the girls for height, weight, waist circumference, Tanner stages of breast and pubic hair development, and menarcheal status. We classified girls as normal weight, overweight, or obese based on BMI, and as normal weight or central obese based on the waist-height ratio, then estimated and compared median age at a given Tanner stage or greater by weight class using Probit models. RESULTS: The median age at menarche was 12.36 years. The median ages at breast stages(B) 2 through 5 were 10.03, 11.38, 13.39, and 15.79 years, respectively, and at pubic hair stages(PH) 2 through 5 were 11.62, 12.70, 14.38, and 16.92 years, respectively. Girls from urban areas experienced menarche, B3 and B4 stages, and PH3 through PH5 stages earlier. Girls with central obesity and overweight/obesity reached puberty earlier at almost every Tanner stage of breast and pubic hair than normal girls. Girls with obesity developed PH2 and PH3 earlier than their overweight peers. However, we did not find any significant differences between girls with overweight and obesity at all stages of breast development. CONCLUSIONS: Childhood obesity, including both overweight/obesity and central obesity, is associated with earlier attainment of puberty in Chinese Han schoolgirls.

Association of the peripheral blood levels of circulating microRNAs with both recurrent miscarriage and the outcomes of embryo transfer in an in vitro fertilization process.

BACKGROUND: Implantation failure is not only a major cause of early pregnancy loss, but it is also an obstacle to assisted reproductive technologies. The identification of potential circulating biomarkers for recurrent miscarriage (RM) and/or recurrent implantation failure would contribute to the development of novel diagnosis and prediction techniques. METHODS: MiR (miR-23a-3p, 27a-3p, 29a-3p, 100-5p, 127-3p and 486-5p) expression in the villi, decidual tissues and peripheral blood plasma and serum were validated by qPCR, and the localization of miRs in the villi and decidual tissues of RM and normal pregnancy (NP) women were detected by in situ hybridization. The invasiveness of HTR8/SVneo cells was determined using a Transwell assay. The predictive values of miRs for RM and the outcome of IVF-ET were respectively calculated by the receiver operating characteristic analysis. RESULTS: The signals of six miRs were observed in the villi and decidual tissues of RM and NP women. The villus miR-27a-3p, miR-29a-3p and miR-100-5p were significantly up-regulated, whereas miR-127-3p and miR-486-5p appeared to be down-regulated in RM women compared to NP women. The invasiveness of HTR8/SVneo cells transfected with miR-23a-3p mimics was evidently weakened, whereas that of cells transfected with miR-127-3p mimics was obviously enhanced. The peripheral blood plasma levels of miR-27a-3p, miR-29a-3p, miR-100-5p and miR-127-3p were significantly increased, whereas that of miR-486-5p was remarkably decreased in RM compared to NP women. By contrast, serum miR-23a-3p and miR-127-3p were significantly decreased, whereas that of miR-486-5p was remarkably increased. The combination of six plasma miRs levels discriminated RM with a sensitivity of 100% and a specificity of 83.3%, whereas that of six serum miRs levels showed a sensitivity of 78.3% and a specificity of 93.1%. In the IVF-ET cohort, the significantly decreased peripheral blood plasma levels of miR-23a-3p, miR-27a-3p, miR-100-5p and miR-127-3p, and the serum levels of miR-100-5p and miR-486-5p, in addition to the significantly increased serum level of miR-27a-3p, were found to be associated with the failure of ET. Moreover, the combination of plasma miR-23a-3p, miR-27a-3p, miR-29a-3p, miR-100-5p, miR-127-3p and miR-486-5p levels discriminated the outcome of IVF-ET with a sensitivity of 68.1% and a specificity of 54.1%, whereas the combination of plasma miR-127-3p and miR-486-5p levels showed a sensitivity of 50.0% and a specificity of 75.3%. CONCLUSIONS: Circulating miR-23a-3p, miR-27a-3p, miR-29a-3p, miR-100-5p, miR-127-3p and miR-486-5 might be involved in RM pathogenesis and present potential diagnostic biomarkers for RM. Meanwhile, these miRs, in particular miR-127-3p and miR-486-5p, provide promising prediction indexes for the outcomes of IVF-ET.

Anorexia nervosa, depression and suicidal thoughts among Chinese adolescents: a national school-based cross-sectional study.

BACKGROUND: Although there is much literature on adolescent suicide, combined effects of depression and anorexia nervosa on suicide were rarely investigated. The aims of this study are to examine the association between anorexia nervosa and suicidal thoughts and explore the interaction between anorexia nervosa and depression. METHODS: This is a cross-sectional study, in the study, a sample of 8,746 Chinese adolescents was selected by multistage stratified method in 2012/2013 from 20 middle schools in 7 provinces across China Mainland. Multilevel logistic model was introduced to explore association between anorexia nervosa and suicidal thoughts. And subgroup analyses were conducted on participants with or without depression. RESULTS: Multilevel logistic model revealed that demographic variables, including academic achievement, were not the predictive risk factors of suicidal thoughts. Those who suffered from worse severity of perceived anorexia nervosa were at increased risk of thinking about suicide. The interaction between depression and anorexia nervosa was significant, however, subgroup analyses showed that the associations were significant only among the adolescents without depression. CONCLUSIONS: Our results indicate that all levels of anorexia nervosa serve as predictable indicators of suicidal thoughts in Chinese adolescents, and the effects of anorexia nervosa are modified by depression status.

Prenatal exposure to antidepressants and risk of epilepsy in childhood.

PURPOSE: This study aimed to estimate the association between prenatal exposure to antidepressants and risk of epilepsy in childhood, taking maternal depression into account. METHODS: We conducted a population-based cohort study including all Danish singletons born alive between 1997 and 2008 (n = 734 237). Information on antidepressant medication and diagnosis of depression and epilepsy was obtained from Danish National Registers. The exposed group comprised children of mothers who used antidepressants from 30 days before pregnancy until the date of birth. The reference group comprised children of mothers who used no antidepressants from 6 months before pregnancy to birth. We estimated the hazard ratios (HR) of epilepsy and 95% confidence intervals (CI) using Cox proportional hazard models. RESULTS: We identified 12 438 (1.7%) children exposed to antidepressants during pregnancy (including 30 days before pregnancy) and 5829 (0.8%) children diagnosed with epilepsy in the follow-up time (mean: 6.7 years). Children exposed to antidepressants during pregnancy had a 27% higher risk of epilepsy (aHR: 1.27; 95%CI: 1.05-1.54) than children in the reference group. The estimate of this association was 1.71 (95%CI: 1.10-2.66) if their mothers also had a registry-based hospital diagnosis of depression in the 6 months before pregnancy or during pregnancy and 1.14 (95%CI: 0.91-1.43) if their mothers had no registry-based hospital diagnosis of depression. Children of mothers who used antidepressants from 2 to 6 months before pregnancy (but not during pregnancy) had an increased risk of epilepsy (aHR: 1.36; 95%CI: 1.07-1.73). CONCLUSIONS: Antidepressant use during pregnancy was associated with a higher risk of epilepsy among children whose mothers had also a registry-based hospital diagnosis of depression during pregnancy. Copyright © 2016 John Wiley & Sons, Ltd.

Expression of artemin and GFRα3 in an animal model of migraine: possible role in the pathogenesis of this disorder.

BACKGROUND: Neurotrophic factors have been implicated in hyperalgesia and peripheral levels of these molecules are altered in migraine pathophysiology. Artemin, a vasculature-derived neurotrophic factor, contributes to pain modulation and trigeminal primary afferent sensitization through binding its selective receptor GFRα3. The distribution of artemin and GFRα3 in the dura mater raises an anatomy supports that they may be involved in migraine. In this study we evaluated the expression of artemin and GFRα3 in an animal migraine model that may be relevant for migraine. METHODS: In this study, using a rat migraine model by administration of nitroglycerin (NTG), we investigated the expression of artemin in the dura mater and GFRα3 in the trigeminal ganglia (TG) by means of quantitative reverse transcription-polymerase chain reaction, western blot and immunofluorescence labeling. RESULTS: Artemin immunoreactivity was found in the smooth muscle cells of dural vasculature and GFRα3 was present in cytoplasm of TG neurons. The mRNA levels of artemin and GFRα3 were significantly elevated after NTG treatment at 2 and 4 h respectively (P < 0.05). The expression of artemin protein was increased at 4 h and continually up to 8 h in the dura mater following NTG administration (P < 0.05). The expression of GFRα3 protein was elevated at 4 h and continually up to 10 h in the TG following NTG administration (P < 0.05). CONCLUSION: The findings suggest that artemin and GFRα3 play an important role in the pathogenesis of migraine and may represent potential therapeutic targets for the treatment of migraine.

Characterizing the binding of annexin V to a lipid bilayer using molecular dynamics simulations.

Annexins play critical roles in membrane organization, membrane trafficking and vesicle transport. The family members share the ability to bind to membranes with high affinities, but the interactions between annexins and membranes remain unclear. Here, using long-time molecular dynamics simulations, we provide detailed information for the binding of an annexin V trimer to a POPC/POPS lipid bilayer. Calcium ions function as bridges between several negatively charged residues of annexin V and the oxygen atoms of lipids. The preferred calcium-bridges are those formed via the carboxyl oxygen atoms of POPS lipids. H-bonds and hydrophobic interactions formed by several critical residues have also been observed in the annexin-membrane interface. The annexin-membrane binding causes small changes of annexin trimer structures, while has significant effects on lipid bilayer structures. The lipid bilayer shows a bent shape and forms a concave region in the annexin-membrane interaction interface, which provides an atomic-level evidence to support the view that annexins could disturb the stability of lipids and bend membranes. This study provides insights into the commonly occurring PS-dependent and calcium-dependent binding of proteins to membranes.

The expression of IL-2 and IL-4 in CD4(+) T cells from mouse lymph nodes and spleen during HSV-1-induced facial palsy.

OBJECTIVE: Herpes simplex virus 1 (HSV-1) is regarded as an important underlying cause of Bell's palsy, but the immunologic mechanism remains unknown. Here, we employed a mouse facial paralysis model to investigate the expressions of CD4(+) T lymphocytes and interleukin (IL)-2 and -4 in the left draining cervical lymph nodes (LCLN) and spleen, as well as the inhibitory effects of glucocorticoids (GCs). METHODS: HSV-1 was inoculated into the surface of the posterior auricle to generate the facial paralysis model. The paralyzed mice were divided into three groups; in one group without any treatment, mice were killed at different time points, and those in the other two groups were injected with methylprednisolone sodium succinate (MPSS) or with a combination of MPSS and GC receptor blocker (RU486). The expression levels of CD4(+) T lymphocytes and CD4(+)-IL-2(+) and CD4(+)-IL-4(+) cells in the LCLN and spleen were detected by fluorescence-activated cell sorting. RESULTS: Expression levels of CD4(+), IL-2, and IL-4 first increased then decreased in LCLN and spleen and peaked 5 and 7 days, respectively, after the manifestation of facial paralysis. All the data at the peak points were significantly different compared with control (p < 0.05), and these effects were inhibited by MPSS. CONCLUSION: Our results suggest that CD4(+), IL-2, and IL-4 participate in the HSV-1-induced facial paralysis immune response. MPSS can effectively attenuate HSV-1-mediated nervous system damage, which is associated with its inhibitory effect on expression of these inflammatory markers.