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In the context of the coronavirus disease 2019 (COVID-19) pandemic, the global healthcare community has raced to find effective therapeutic agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, dexamethasone is the first and an important therapeutic to significantly reduce the risk of death in COVID-19 patients with severe disease. Due to powerful anti-inflammatory and immunosuppressive effects, dexamethasone could attenuate SARS-CoV-2-induced uncontrolled cytokine storm, severe acute respiratory distress syndrome and lung injury. Nevertheless, dexamethasone treatment is a double-edged sword, as numerous studies have revealed that it has significant adverse impacts later in life. In this article, we reviewed the literature regarding the adverse effects of dexamethasone administration on different organ systems as well as related disease pathogenesis in an attempt to clarify the potential harms that may arise in COVID-19 patients receiving dexamethasone treatment. Overall, taking the threat of COVID­19 pandemic into account, we think it is necessary to apply dexamethasone as a pharmaceutical therapy in critical patients. However, its adverse side effects cannot be ignored. Our review will help medical professionals in the prognosis and follow-up of patients treated with dexamethasone. In addition, given that a considerable amount of uncertainty, confusion and even controversy still exist, further studies and more clinical trials are urgently needed to improve our understanding of the parameters and the effects of dexamethasone on patients with SARS-CoV-2 infection.

To examine the effect of pre-pregnancy maternal body mass index (BMI) on neonatal weight outcomes of twin infants who were conceived by assisted reproductive technology (ART). A 10-year (2006–2015) Chinese sample of 3431 mothers and their twin infants conceived by ART from a retrospective cohort were included. The effects of pre-pregnancy maternal BMI on gestational age and birth weight were assessed by generalized linear model and generalized estimating equation model. Compared with a normal weight group, pre-pregnancy maternal underweight was associated with lower birth weight and increased risk of small for gestational age (SGA) in twins conceived by ART (birth weight: difference −59.22 g, 95% CI −93.16 to −25.27 g; SGA: RR 1.25, 95% CI 1.09 to 1.43). Pre-pregnancy maternal obesity was associated with higher birth weight and increased risk of preterm birth (birth weight: difference 65.82 g, 95% CI 10.66 to 120.99 g; preterm birth: RR 1.19, 95% CI 1.03–1.37). A nonlinear relationship between pre-pregnancy maternal BMI and SGA was observed. The risk of SGA decreased with the pre-pregnancy maternal BMI up to the turning point (BMI = 21) (RR 0.90, 95% CI 0.86–0.95). Among mothers undergoing ART, pre-pregnancy maternal obesity is associated with higher birth weight and higher risk of preterm birth for twin pregnancy, and pre-pregnancy maternal underweight is associated with lower birth weight and higher risk of SGA. Women preparing for ART should maintain a normal BMI to lower the chances of adverse neonatal outcomes.

Summary The diffuse-type gastric cancer (DGC) constitutes a subgroup of gastric cancer with poor prognosis and no effective molecular therapies. Here, we report a phosphoproteomic landscape of DGC derived from 83 tumors together with their nearby tissues. Based on phosphorylation, DGC could be classified into three molecular subtypes with distinct overall survival (OS) and chemosensitivity. We identified 16 kinases whose activities were associated with poor OS. These activated kinases covered several cancer hallmark pathways, with the MTOR signaling network being the most frequently activated. We proposed a patient-specific strategy based on the hierarchy of clinically actionable kinases for prioritization of kinases for further clinical evaluation. Our global data analysis indicates that in addition to finding activated kinase pathways in DGC, large-scale phosphoproteomics could be used to classify DGCs into subtypes that are associated with distinct clinical outcomes as well as nomination of kinase targets that may be inhibited for cancer treatments., Graphical Abstract, Highlights • A phosphoproteomic landscape of diffuse-type gastric cancer (DGC) was depicted • DGC could be classified into three subtypes based on phosphorylation data • A bioinformatics workflow was used to identify 16 kinases as potential drug targets • A patient-specific strategy for nomination of kinases was proposed, Biological Sciences; Cancer Systems Biology; Proteomics; Systems Biology

Purpose A small number of risk prediction model have been previously reported to predict the infertility treatment success. While the studies of the risk prediction model for the patients with low prognosis are limited. This study aimed to construct and validate a nomogram for the prediction of cumulative live birth rate (CLBR) in patients with low prognosis from a single center database in Chinese population. Methods Clinical data of 4,395 patients with low prognosis, who received in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) therapy between 2014 and 2018, were retrieved and randomly divided into training (70%) and the external validation (30%) sets. Multivariate analysis with logistic regression model was conducted. Results Multivariate analyses showed that maternal age, body mass index (BMI), basal serum follicle-stimulating hormone (FSH) level, type of infertility, male factors, uterine factors, and usable embryos number at day 3 were risk factors for CLBR in patients with low prognosis. The area under the receiver operating characteristic curve (AUC) of the prediction model was 0.769 (95% confident interval (CI): 0.751, 0.787) in training set. The validation set presented good performance with an AUC of 0.749 (95% CI: 0.720, 0.778). In addition, Hosmer-Lemeshow chi-square value was 10.194 (P = 0.252). Conclusion We constructed and validated a nomogram for the prediction of CLBR in low prognosis patients with a single center database in Chinese population. The validated nomogram for the prediction of CLBR could be potentially applied in clinic for IVF counselling in patients with low prognosis.

Pulsed dye laser (PDL) is the first line treatment for port wine stain (PWS). However, only a small portion of the lesions could be completely cleared by PDL treatment, which might be related to the regeneration and revascularization of the vascular structures after laser irradiation. Recently, it is believed that the suppression of regeneration and revascularization of photocoagulated blood vessels can achieve a better therapeutic outcome. We use rabbit ear and SD rat as the animal models to investigate whether PDL-induced angiogenesis can be suppressed by topical metformin. Our results showed that topical application of metformin can effectively suppress the PDL-induced early stage of angiogenesis via inhibition of the AKT/mTOR/P70S6K pathway in animal models.

ObjectiveTo investigate the association between pre-pregnancy body mass index (BMI) and miscarriages in women who required assisted reproductive technology (ART) for conception.MethodsA retrospective cohort study was conducted using a 10-year (2006–2015) sample of 14,994 pregnancy cycles with ART treatment in Northwest Women’s and Children’s Hospital, Xi’an, China. The effects of women’s BMI before pregnancy on early miscarriage and miscarriage were assessed using generalized estimating equation models.ResultsThe risks of early miscarriage and miscarriage were higher in the obese group than in the normal weight group [early miscarriage: relative risk (RR) = 1.36, confidence interval (CI): 1.12–1.65; miscarriage: RR = 1.40, 95% CI: 1.17–1.68]. Pre-pregnancy underweight was not associated with an increased risk of early miscarriage or miscarriage. We observed interactions between pre-pregnancy BMI and singleton or twin pregnancy in early miscarriage and miscarriage (P = 0.017 and P = 0.003, respectively). Twin pregnancy increased the effects of pre-pregnancy BMI on early miscarriage and miscarriage (early miscarriage: a. singleton pregnancy: RR = 1.02, 95% CI: 1.01–1.04; b. twin pregnancy: RR = 1.08, 95% CI: 1.03–1.13; miscarriage: a. singleton pregnancy: RR = 1.02, 95% CI: 1.01–1.04; b. twin pregnancy: RR = 1.08, 95% CI: 1.05–1.13).ConclusionsPre-pregnancy obesity was associated with higher risks of early miscarriage and miscarriage in the ART population, and twin pregnancy increased the effects of pre-pregnancy BMI on early miscarriage and miscarriage. Women should maintain a normal BMI before ART initiation to prevent adverse pregnancy outcomes.

To compare the clinical outcome of fresh embryo transfer with frozen-thawed embryo transfer in subsequent cycle of GnRH antagonist protocol. Totally, 1430 women were enrolled from the cases of our Assisted Reproduction Center from January 2015 to January 2019 for this retrospective cohort study. The inclusion criteria of the subjects included women with ages under 40 years, 3–10 oocytes retrieved, good embryo quality according to gardener score, GnRH antagonist protocol, underwent first cycle of fresh embryo transfer or freeze-all strategy and transferred in subsequent cycle. However, the patients with endometriosis, PGD/PGS cycles, history of recurrent pregnancy loss and uterine pathology were excluded. 495 women of group I underwent fresh embryo transfer in first cycle and 935 patients of group II received frozen-thawed transfer in subsequent cycle. The primary outcome was clinical pregnancy rate. A logistic regression analysis was performed to determine the variables that could be independently associated with clinical pregnancy rate. Models were adjusted for covariates including patients’ age, fertilization type, infertility type, infertility duration, the number of oocytes retrieved, the number of embryos transferred and type of embryo transferred. Clinical pregnancy rate was significantly higher in frozen-thawed embryo transfer than in fresh embryo transfer (63.70% vs. 54.50%, p

Research question Is pre-pregnancy maternal underweight associated with perinatal outcomes of singletons who were conceived through assisted reproductive technology (ART)? Design A 10-year (2006–2015) Chinese sample of 6538 women and their singleton infants who were conceived through ART was used to examine the association between pre-pregnancy maternal underweight and perinatal outcomes. Propensity scores for underweight were calculated for each participant using multivariable logistic regression, which was used to match 740 (91.36% of 810) underweight women with 740 normal weight women; the effects of underweight on birth weight and gestational age were then assessed by generalized estimating equation model. Results After propensity score matching, the birth weight was lower (difference –136.83 g, 95% CI –184.11 to –89.55 g) in the underweight group than in the normal weight group. The risks of low birth weight (LBW) and small for gestational age (SGA) were increased in the underweight group compared with those in the normal weight group (LBW: RR 1.64, 95% CI 1.01 to 2.67; SGA: RR 1.46, 95% CI 1.06 to 2.02). The risks of fetal macrosomia and being large for gestational age (LGA) were decreased in the underweight group compared with those in the normal weight group (macrosomia: RR 0.39, 95% CI 0.26 to 0.61; LGA: RR 0.36, 95% CI 0.24 to 0.53). The associations between underweight, gestational age and preterm birth were not statistically significant. Conclusions Among women undergoing ART, pre-pregnancy maternal underweight was associated with lower birth weight, increased LBW and SGA risks, and decreased fetal macrosomia and LGA risks in singleton infants.

Are there greater risks of adverse perinatal outcomes, in particular of congenital malformations, after blastocyst transfer compared with cleavage-stage embryo transfer in IVF?This was a retrospective cohort analysis from a centre for assisted reproduction at a public hospital in China over the period 2006-2015. The analysis covered all women who conceived (15,254) and newborns (16,213) from IVF/intracytoplasmic sperm injection (ICSI) cycles with cleavage-stage embryo transfer or blastocyst transfer. The principal outcome measures were congenital malformations, preterm birth (PTB), low birthweight (LBW), small for gestational age (SGA) and large for gestational age (LGA).Logistic regression analysis showed that the sex ratio was imbalanced towards male neonates after blastocyst transfer (P=0.001; adjusted OR 1.17, 95%CI 1.07-1.30) but there were no differences in rates of miscarriage, ectopic pregnancy, stillbirth, very preterm birth (32 weeks), PTB (37 weeks), LBW, SGA or LGA between blastocyst transfer and cleavage-stage embryo transfer. A total of 176 congenital malformations (123 cleavage-stage embryos versus 53 blastocysts) were identified both in newborns and aborted fetuses, but the difference between groups was not statistically significant.There was no difference in the risks of adverse perinatal outcomes, and in particular of congenital malformation, after blastocyst transfer compared with cleavage-stage transfer, although there was a sex ratio imbalance towards male neonates after blastocyst transfer.

Pathogens that cause respiratory diseases in poultry are highly diversified, and co-infections with multiple pathogens are prevalent. The H9N2 strain of avian influenza virus (AIV) and Escherichia coli (E. coli) are common poultry pathogens that limit the development of the poultry industry. This study aimed to clarify the interaction between these two pathogens and their pathogenic mechanism using a mouse model. Co-infection with H9N2 AIV and E. coli significantly increased the mortality rate of mice compared to single viral or bacterial infections. It also led to the development of more severe lung lesions compared to single viral or bacterial infections. Co-infection further causes a storm of cytokines, which aggravates the host’s disease by dysregulating the JAK/STAT/SOCS and ERK1/2 pathways. Moreover, co-infection mutually benefited the virus and the bacteria by increasing their pathogen loads. Importantly, nitric oxide synthase 2 (NOS2) expression was also significantly enhanced by the co-infection. It played a key role in the rapid proliferation of E. coli in the presence of the co-infecting H9N2 virus. Therefore, our study underscores the role of NOS2 as a determinant for bacteria growth and illustrates its importance as an additional mechanism that enhances influenza virus-bacteria synergy. It further provides a scientific basis for investigating the synergistic infection mechanism between viruses and bacteria.

Background An increased incidence of monozygotic twinning after a blastocyst transfer has been previously reported in assisted reproductive technology treatment. It is uncertain whether this phenomenon is due to the extended culture time, culture medium, or inherent blastocyst parameters. Objective This study aimed to investigate the association between blastocyst parameters (in vitro culture time, blastocyst stage, and inner cell mass and trophectoderm grading) and the incidence of monozygotic twinning after assisted reproductive technology. Study Design This was a retrospective cohort study employing data from a multicenter, large, electronic database from 4 academic hospitals. All clinical pregnancies after a single blastocyst transfer between January 2014 and February 2020 were included. Blastocyst morphology was evaluated based on the Gardner grading system, considering the blastocyst stage, and inner cell mass and trophectoderm grading (grades A, B, and C). Monozygotic twinning was defined as ≥2 fetal heartbeats in a single gestational sac or 2 gestational sacs with sex concordance at birth. The multivariable predicted marginal proportions from logistic regression models were used to compute adjusted relative risks for the association between blastocyst parameters and the incidence of monozygotic twinning. Results The overall monozygotic twinning rate was 1.53% (402 of 26,254 cases). The monozygotic twinning was not associated with the culture time in vitro (day 5 vs day 6) or blastocyst stage (early, blastocyst, expanded, hatching, and hatched). Alternatively, monozygotic twinning was associated with lower inner cell mass grading (B vs A: adjusted relative risk, 1.67 [95 % confidence interval, 1.28–2.25]; C vs A: adjusted relative risk, 1.98 [95% confidence interval, 1.18–3.11]) and higher trophectoderm grading (B vs C: adjusted relative risk, 1.38 [95% confidence interval, 1.03–1.92]; A vs C: adjusted relative risk, 2.14 [95% confidence interval, 1.45–3.20]). The incidence of monozygotic twinning was the lowest in blastocysts with grade A inner cell mass and grade B or C trophectoderm (0.82%, as the reference) and the highest in blastocysts with grade B or C inner cell mass and grade A trophectoderm (2.40%; adjusted relative risk, 2.62; 95% confidence interval, 1.60–4.43). The incidence of monozygotic twinning in blastocysts with consistent inner cell mass or trophectoderm grading was somewhere in between (both A: 1.58%; adjusted relative risk, 1.86 [95% confidence interval, 1.23–3.04]; both B or C: 1.59%; adjusted relative risk, 1.84 [95% confidence interval, 1.29–2.90]). Conclusion Higher risk of monozygotic twinning was associated with blastocyst morphology specific to those blastocysts with loosely arranged inner cell mass cells combined with tightly packed trophectoderm cells.

Influenza virus is a highly contagious zoonotic respiratory disease that causes seasonal outbreaks each year and unpredictable pandemics occasionally with high morbidity and mortality rates, posing a great threat to public health worldwide. Besides the limited effect of vaccines, the problem is exacerbated by the lack of drugs with strong antiviral activity against all flu strains. Currently, there are two classes of antiviral drugs available that are chemosynthetic and approved against influenza A virus for prophylactic and therapeutic treatment, but the appearance of drug-resistant virus strains is a serious issue that strikes at the core of influenza control. There is therefore an urgent need to develop new antiviral drugs. Many reports have shown that the development of novel bioactive plant extracts and microbial extracts has significant advantages in influenza treatment. This paper comprehensively reviews the development and effects of chemosynthetic drugs, plant extracts, and microbial extracts with influenza antiviral activity, hoping to provide some references for novel antiviral drug design and promising alternative candidates for further anti-influenza drug development.

Objective: To investigate the mental health of women undergoing assisted reproductive technology (ART) treatment during the novel coronavirus pneumonia (COVID-19) pandemic outbreak in Xi'an, China.Methods: A repeated cross-sectional study was administered to women undergoing ART treatment during the outbreak period (599 women in February 2020) and the control period (892 women in May 2020) at the Northwest Women's and Children's Hospital, Xi'an, China.Results: Both the ART-treated women surveyed during the outbreak period and those surveyed during the control period had high scores on the fear dimension (0.88, 0.51). The total scores for mental health among the participants during the control period were lower than those during the outbreak period (difference = −0.22; 95% CI = −0.25, −0.18). Lower scores were also seen during the control period, compared to those in the outbreak period, for depression (difference = −0.18; 95% CI = −0.23, −0.13), neurasthenia (difference = −0.31; 95% CI = −0.36, −0.25), fear (difference = −0.37; 95% CI = −0.43, −0.31), compulsion anxiety (difference = −0.13; 95% CI = −0.16, −0.09), and hypochondriasis (difference = −0.09; 95% CI = −0.12, −0.06).Conclusions: During the COVID-19 global pandemic, the mental health of women undergoing ART treatment in Xi'an, China, was primarily manifested as fear. As the pandemic was brought under control, the mental health of ART-treated women improved. As evidenced by these results, the COVID-19 pandemic influences the mental health of women undergoing ART treatment, and clinicians should be aware of this for similar future situations.

Filaggrin, encoded by the FLG gene, plays a crucial role in the barrier function of epidermis, but the association between FLG loss-of-function mutations and infectious skin diseases has not been systematically studied. FLG coding sequences from 945 patients with leprosy and 916 healthy controls were captured and enriched using an array-based high-throughput system, and subjected to next-generation sequencing. The loss-of-function mutations found were further validated by Sanger sequencing. A total of 21 loss-of-function mutations were found in 945 patients with leprosy, with a carrier rate of 17.53%, while the prevalence of these mutations in 916 healthy controls was 14.77%, which was significantly lower than in patients. Two individual FLG loss-of-function mutations (K4022X and Q1790X) were found to be significantly associated with leprosy. These results suggest a possible role for filaggrin in defending against leprosy pathogens.

Objective: To demonstrate the association between pre-pregnancy maternal overweight, obesity, and perinatal outcomes of singletons conceived by assisted reproductive technology (ART). Design: Retrospective cohort study from 2006 to 2015 data from a single ART center. Setting: Assisted Reproduction Center, Northwest Women's and Children's Hospital, Xi'an, Northwestern China. Patients: We included 7,818 women undergoing ART and their singleton infants. Interventions: None. Main Outcome Measure: The primary outcome measures were preterm birth (PTB), macrosomia, low birth weight, small for gestational age, and large for gestational age (LGA). Results: We experienced an increase in the risk of PTB, macrosomia, and LGA in overweight and obese groups compared with that in normal-weight groups [PTB: overweight vs. normal weight: odds ratio [OR] = 1.44, 95% CI: 1.18–1.75; obesity vs. normal weight: OR = 1.53, 95% CI: 1.04–2.25; macrosomia: overweight vs. normal weight: OR = 1.78, 95% CI: 1.48–2.14; obesity vs. normal weight: OR = 2.16, 95% CI: 1.52–3.06; LGA: overweight vs. normal weight: OR = 1.63, 95% CI: 1.39–1.90; obesity vs. normal weight: OR = 2.11, 95% CI: 1.57–2.83]. We observed a significant interaction between maternal BMI and fresh/frozen embryo transfer on PTB and LGA (P = 0.030; P = 0.030). Fresh embryo transfer significantly increased the effect of maternal BMI on LGA (fresh: OR = 1.14, 95% CI: 1.10–1.18; frozen: OR = 1.09, 95% CI: 1.04–1.13), and frozen embryo transfer increased the effect of maternal BMI on PTB (fresh: OR = 1.03, 95% CI: 0.99–1.08; frozen: OR = 1.09, 95% CI: 1.04–1.15). Conclusions: Pre-pregnancy maternal overweight and obesity were associated with higher risks of PTB, macrosomia, and LGA in ART-conceived singletons. These associations were affected by the timing of embryo transfer (fresh/frozen embryo transfer). Therefore, we recommend women before ART to maintain a normal BMI for the prevention of adverse perinatal outcomes.

Objective To investigate ovarian sensitivity in subgroups of patients with a low prognosis, as defined by the POSEIDON criteria, undergoing in vitro fertilization treatment and measures to improve ovarian sensitivity in these patients. Design We conducted a retrospective cohort analysis. Setting The study was conducted at an IVF clinic in a public hospital. Patients A total of 32,128 fresh IVF cycles from January 2014 to October 2018 at a single IVF clinic were included in the analysis. Patients with a low prognosis were categorized into four groups based on the POSEIDON criteria. Interventions None. Main outcome measure The primary outcome measures were the follicular output rate (FORT) and the follicle-to-oocyte index (FOI). Results The FORTs in the order from the highest to the lowest were 1.18 in group 3, 0.98 in group 4, 0.76 in group 1, and 0.68 in group 2. The trend in the FOI values was consistent with that in the FORTs. Among patients with poor ovarian sensitivity, 58.41% of patients with FORTs ≥ 0.30 in the second cycle underwent an adjustment to the ovarian stimulation (OS) protocol and 41.59% underwent an adjustment to the gonadotropin (Gn) starting dose. Among patients with normal ovarian sensitivity, 43.56% of those with FORTs ≥ 0.80 in the second cycle underwent an adjustment to the OS protocol and 56.44% underwent an adjustment to the Gn starting dose. Conclusion Ovarian sensitivity was the highest in group 3 (young women with poor ovarian reserve), followed by groups 4 (women at advanced age with poor ovarian reserve) and 1 (young women with good ovarian reserve), and it was the lowest in group 2 (women at advanced age with good ovarian reserve). For patients with poor ovarian sensitivity, it is preferred to recommend an adjustment to the OS protocol, while for those with normal ovarian sensitivity, adjusting the Gn starting dose is preferred.

Post-translational modification of proteins by the addition of small ubiquitin-related modifier (SUMO) is a dynamic process, in which deSUMOylation is carried out by members of the Sentrin/SUMO-specific protease (SENP) family. While identification of SUMOylation sites at global scale has made great progress, much less effort has been made on the SENP family-dependent deSUMOylation. Here we report a dataset of 3,763 high confident SUMO1 modification sites and their dependence on the 6 members of SENP proteins. Interrogation of the dataset led to the discovery that SENP3 regulates the innate immune response via deSUMOylation of DHX15 and PCBP2 and recruitment of inflammatory molecules. Collectively, this dataset presents a site-resolved network of the SUMO-SENP system, providing information for potential substrates of the SENP proteins.

It is unknown whether seasonal variation influences the outcome of in vitro fertilization (IVF). Previous studies related to seasonal variation of IVF were all small sample size, and the results were conflicting. We performed a retrospective cohort study evaluating the relationship between seasonal variability and live birth rate in the year of 2014–2017. Patients were grouped into four seasons (Winter (December-February), Spring (March-May), Summer (June-August), and Autumn (September-November)) according to the day of oocyte pick-up (OPU). Multivariate logistic regression analysis was performed to evaluate association between seasonal variation and live birth. Models were adjusted for covariates including temperature, sunshine hour, infertility type, infertility duration, infertility factor and BMI. In total 38,476 women were enrolled, of which 25,097 underwent fresh cycles, 13,379 were frozen embryo transfer. Live birth rates of fresh embryo transfer were 50.36%, 53.14%, 51.94% and 51.33% for spring, summer, autumn and winter, respectively. Clinical pregnancy rate between the calendar months varied between 55.1% and 63.4% in fresh embryo transfer (ET) and between 58.8% and 65.1% in frozen embryo transfer (FET) (P-values 0.073 and 0.220). In the unadjusted model and adjust model, seasonal variation was not associated with live birth. In conclusion, there was no significant difference of seasonal variations in the outcome of IVF with fresh embryo transfer and frozen embryo transfer.

In this paper, the types, formation time, structural morphology, and influence of steel corrosion products in seawater and sea-sand concrete were studied, and the intermediate and final products of steel corrosion under different conditions were determined. The corrosion products of steel in these concrete specimens under two curing methods were studied separately by X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). Due to the presence of a large amount of chloride ions in the concrete, the rust layer on the surface of a steel bar contained many intermediates, such as lepidocrocite (&gamma, &ndash, FeOOH) and aka-ganeite (&beta, FeOOH). Under wet/dry cycles, with the addition and loss of moisture in concrete, various corrosion products were also dynamically converted into each other. In the specimens immersed in seawater for a long time, the intermediates of corrosion were lepidocrocite (&gamma, FeOOH), which were substituted for oxygen as the new depolarizers of cathode reduction reaction, and consumed themselves to ensure smooth corrosion.

Objective To determine the optimal endometrial preparation protocols of frozen-thawed embryo transfer (FET) in young women with regular menstrual cycles. Design Retrospective cohort study. Setting Public fertility center. Patient(s) Infertile women with regular menstrual cycles undergoing FET. Intervention(s) Natural cycle (NC) treatment for patients with proven ovulation in previous cycles or who refused medication (n = 308), or hormone treatment (HT) for patients who could not be frequently monitored (n = 1,538). Main Outcome Measure(s) Live-birth rates. Result(s) The live-birth rates were 61.73% in the NC group and 55.11% in the HT group. The effect size of the endometrial preparation on live-birth rates was evaluated in prespecified and exploratory subgroups in each subgroup, and multivariable logistic regression analysis was used to determine which variables could be independently associated with the live-birth rate. The HT patients had a lower chance of live birth in all subgroups: endometrial thickness on the day of progesterone administration, triple-line endometrial pattern, female age at embryo transfer, fertilization type, and protocol in the fresh cycle. Multivariable analysis showed NC to be associated with an increased likelihood of live birth compared with HT. Conclusion(s) Natural cycle treatment has a higher chance of live birth than HT for endometrial preparation in young women with regular menstrual cycles.

In this paper, the effect of chloride ions on the development of corrosion pits in different reinforced concrete under different environmental conditions is studied. A fitting model for the size distribution of pits in seawater and sea-sand concrete (SSC) under different curing modes is established, and time-dependent fractal features are examined. Under wet/dry chloride cycles, the weight loss rate and corrosion rate of steel bars are higher, and the number of corrosion pits appears to increase on a small scale within 60-day. A majority of the corrosion is metastable pitting, and we propose a model to describe the size distribution of pitting in different periods. The good agreement between the proposed model and the available data illustrates that the proposed model is reliable and accurate. Macroscopic pitting occurs first in wet/dry chloride cycles. With the increase of concrete age, the size distribution of pits under wet/dry chloride cycles is uneven, and the pit sizes in submerged concrete tend to be equal.

The association between folic acid supplementation and birth defects other than neural tube defects remains unclear. We utilized data from a large population-based survey to examine the association between folic acid supplementation and birth defects in Northwestern China. A total of 29,204 women with infants born between 2010 and 2013 were surveyed in Shaanxi province, Northwestern China, using a stratified multistage sampling method. Propensity scores were used to match 9,293 women with optimal folic acid supplementation with 9,293 women with nonoptimal folic acid supplementation, and the effects of optimal folic acid supplementation on birth defects were assessed by a conditional logistic regression model. After propensity score matching, the overall birth defect rate, cardiovascular system defect rate and nervous system defect rate for the women with optimal folic acid supplementation were lower than those for the women with nonoptimal folic acid supplementation (overall birth defects: OR = 0.71, 95% CI = 0.57–0.89, P = 0.003; cardiovascular system defects: OR = 0.65, 95% CI = 0.44–0.96, P = 0.032; nervous system defects: OR = 0.13, 95% CI = 0.02–0.99, P = 0.049). Optimal folic acid supplementation was associated with a decreased prevalence of birth defects, especially in the cardiovascular system and nervous system. Our findings have important implications for birth defect intervention with folic acid supplementation for countries with a high prevalence of birth defects, such as China.

The ectopic pregnancy (EP) rate after in vitro fertilization-embryo transfer (IVF-ET) is higher than after spontaneous conception. The reason for the increased risk of EP is not clear. We aimed to determine the risk factors associated with EP in patients undergoing IVF-ET.This was a 1:4 matched case-control study that enrolled 225 EP patients and 900 matched intrauterine pregnancy patients from the ART center of Northwest Women's and Children's Hospital from January 2014 to April 2018. Conditional logistic regression was used to analyze the association between risk factors and EP, and a receiver-operating characteristic (ROC) curve was generated for the predictors of EP.Our findings showed that tubal factor (OR 1.61; 95% CI 1.12-2.31) and pelvic surgery other than cesarean section (OR 2.04; 95% CI 1.26-3.29) were associated with a higher risk of EP (p = 0.001). An endometrial thickness 12 mm prior to embryo transfer (OR 0.27; 95% CI 0.13-0.56) and the number of transferable embryos (OR 0.71; 95% CI 0.65-0.78) were protective factors against EP (p 0.001). The other factors did not have a significant effect on the probability of developing ectopic pregnancy. The area under the curve of the endometrial thickness and the number of transferable embryos for EP prediction were higher than those for tubal factor and pelvic surgery other than cesarean section.An endometrial thickness 12 mm is a strong protective factor against ectopic pregnancy. Attention should be paid to women with specific characteristics who have undergone IVF-ET.

Au/ZnO microwire Schottky diodes are fabricated. The devices exhibit typical Schottky diode I–V behavior with a turn-on voltage of about 0.72 V. The hexagonal ZnO microwires act as whispering gallery mode (WGM) lasing microcavities. Under forward bias, a three-microwire device exhibits WGM ultraviolet lasing spectra with a quality factor of about 1287. Output power of the laser has been measured at various injection currents, indicating threshold behavior with a threshold current of about 59 mA. Due to limited hole injection in the operation of Schottky diode, the lasing is a result of an excitonic recombination within the WGM cavity.

To analyze the three pro-nuclei (3PN) incidence on clinical outcomes of patients with lower retrieved oocytes in the fresh cleavage-stage embryo transfer (ET) cycles.This study included 1200 fresh cleavage-stage ET cycles from January 2013 to June 2015. The patients were divided into 3PN = 0% (773 cycles) and 3PN 0% (427 cycles) group. Main outcomes compared were fertilization, cleavage, normal fertilization, good quality embryo, implantation, clinical pregnancy, and early abortion rate.We observed that there was no significant difference in female's age, the number of retrieved oocytes, the number of transferred embryos, the number of good quality embryos, endometrial thickness, infertile time, basal serum follicle-stimulating hormone, and E2 value between two groups (p 0.05). The fertilization (89.43 versus 83.90%, p 0.001) and cleavage (98.34 versus 97.19%, p = 0.048) rates were significantly higher in 3PN 0% than 3PN = 0% group. However, the normal fertilization (70.05 versus 50.67%, p 0.001), good quality embryos (37.11 versus 26.47%, p 0.001), and clinical pregnancy (49.81 versus 43.79%, p = 0.046) rates were significantly higher in 3PN = 0% than 3PN 0% group. The implantation (35.88 versus 33.78%, p = 0.333) and early abortion (8.83 versus 10.70%, p = 0.474) rates were not significantly different between two groups.3PN incidence might make a negative effect on clinical outcomes for patients with lower retrieved oocytes in the fresh cleavage-stage ET cycles.

To evaluate the effect of atmospheric oxygen (O2) concentration on embryonic development, a controlled and randomized study using the sibling oocytes was carried out. A total of 147 patients were studied. Embryos were cultured in O2 concentration 20% versus 5% during the gamete, zygote, and first 3 days. The mean cell numbers of embryo (7.69 ± 1.91 vs 7.20 ± 1.82, P = .011) and rate of clinically useable embryos (81.62% vs 77.22%, P = .017) were significantly higher in 5% O2 than in 20% O2. There was no difference in the zygote developmental stage, day 2, day 4, and blastocyst stage. The quality of blastocyst (both inner cell mass and trophectoderm) showed no difference. Also, there was no increase in embryos fragmentation and uneven cells in 20% O2 culture condition. In conclusion, 20% O2 reduced the mean cell numbers of embryo and the number of clinically useable embryos on day 3. However, there was no subsequent negative impact on development of day 4 and blastocyst stage.

Centromere protein I (CENPI),an important member of centromere protein family, has been suggest to serve as a oncogene in breast cancer, but the clinical significance and biological function of CENPI in colorectal cancer (CRC) is still unclear. In our results, we found CENPI was overexpressed in CRC tissues and cells, and associated with clinical stage, tumor depth, lymph node metastasis, distant metastasis and differentiation in CRC patients. However, there was no significant association between CENPI protein expression and overall survival time in colon cancer patients and rectal cancer patients through analyzing TCGA survival data. Moreover, CENPI mRNA and protein were increased in metastatic lymph nodes compared with primary CRC tissues. Down-regulation of CENPI expression suppresses CRC cell migration, invasion and epithelial mesenchymal transition process. In conclusion, CENPI is overexpressed in CRC and functions as oncogene in modulating CRC cell migration, invasion and EMT process.

Metastasis is the main cause of death in cancer patients. TGF-β is pro-metastatic for malignant cancer cells. Here we report a loss-of-function screen in mice with metastasis as readout and identify OTUD1 as a metastasis-repressing factor. OTUD1-silenced cancer cells show mesenchymal and stem-cell-like characteristics. Further investigation reveals that OTUD1 directly deubiquitinates the TGF-β pathway inhibitor SMAD7 and prevents its degradation. Moreover, OTUD1 cleaves Lysine 33-linked poly-ubiquitin chains of SMAD7 Lysine 220, which exposes the SMAD7 PY motif, enabling SMURF2 binding and subsequent TβRI turnover at the cell surface. Importantly, OTUD1 is lost in multiple types of human cancers and loss of OTUD1 increases metastasis in intracardial xenograft and orthotopic transplantation models, and correlates with poor prognosis among breast cancer patients. High levels of OTUD1 inhibit cancer stemness and shut off metastasis. Thus, OTUD1 represses breast cancer metastasis by mitigating TGF-β-induced pro-oncogenic responses via deubiquitination of SMAD7., The activation of TGF-β signaling has been implicated in cancer metastasis. Here, the authors show that OTUD1 suppresses metastasis by antagonizing the TGF-β pathway via the deubiquitination of SMAD7, and its loss correlates with poor prognosis in breast cancer.

Purpose: We mainly aimed to compare the incidence of embryonic arrest between fresh embryo and frozen-thawed embryo transfers. Methods: This study included 4592 fresh embryo and 4461 frozen-thawed embryo transfers. In fresh embryo transfers, it included 3003 cleavage-stager embryo and 1589 blastocyst-stage embryo transfers. In frozen-thawed embryo transfers, it included 1626 cleavage-stager embryo and 2835 blastocyst-stage embryo transfers. Main clinical outcomes: embryonic arrest rate. Results: Fresh embryo transfers had a lower embryonic arrest rate than frozen-thawed embryo transfers, with statistically significant difference (6.08 versus 7.20%; p=0.032). However, in cleavagestage embryo transfers, fresh group and frozen-thawed group had no significant difference in the embryonic arrest rate (6.59 versus6.95%; p=0.644). We also observed that the embryonic arrest rate was no significant difference between cleavage-stage embryo and blastocyst-stage embryo transfers (6.72 versus 6.53%; p=0.722). More interestingly, single cleavage-stage embryo transfers had a higher embryonic arrest rate compared with single blastocyst-stageembryo transfers (8.13 versus 4.67%; p=0.010). Conclusions: Embryonic development is more likely to happen in frozen-thawed embryo transfers. Frozen-thawed embryo transfers might not be a superior choice to patients with prior embryonic arrest. Extended culture to blastocyst-stage might be a superior therapy to another fresh cycle in patients with prior embryonic arrest.

Metal-semiconductor-metal devices were fabricated by utilizing MgZnO thin films to demonstrate random lasing in the deep ultraviolet wavelength range tuned by Mg content in the film. Room temperature lasing is realized in the wavelength range down to 284 nm.

There is no sufficient data to conclude the benefit of assisted hatching (AH) for advanced age patients. However, AH is routinely performed for advanced age patients undergoing in vitro fertilization (IVF) in China based on some retrospective evidence. It is important to assess the benefit of AH procedure for advanced age patients, especially by analyzing the data from China. This is a prospective randomized controlled trial to evaluate the effect of laser AH in the advanced age patients undergoing IVF. A total of 256 patients conformed to the inclusion criteria, and 78 were excluded by exclusion criteria. A total of 178 patients were eligible and randomized to 2 groups (82 AH group and 96 control group). Laser AH (zona thinning) was performed in the AH group. There were no statistical significance in basic clinical parameters between the 2 groups. No difference was found in implantation rate (AH vs control, 32.45% vs 39.29%) and clinical pregnancy rate (AH vs control, 48.78% vs 59.38%). Our data did not find any benefit of laser AH in improving implantation or pregnancy rates in advanced age women. Due to the potential risk and increasing financial burden, AH should not be routinely performed in first fresh IVF embryo transfer cycle for advanced age women.

Objective To evaluate the safety of vitrification of embryos by comparing the perinatal outcome of vitrified day 3 ETs with fresh cleavage-stage ETs. Design Retrospective analysis. Setting Assisted reproduction center. Patient(s) A total of 806 women with 494 infants delivered were included. Intervention(s) Supernumerary embryos and embryos of patients at risk of ovarian hyperstimulation syndrome were vitrified using a Cryotop carrier in an open system and were transferred after warming. Main Outcome Measure(s) Implantation and pregnancy rates, obstetric outcomes, neonatal outcomes, and congenital birth defects. Result(s) A total of 2,543 vitrified embryos were warmed, and 2,375 survived and were transferred. The implantation, pregnancy, miscarriage, and live birth rates were 26.91%, 47.22%, 6.07%, and 38.58%, respectively. In singletons, the mean birth weight was 3,337.44 g, and the mean Apgar scores were 8.91, 9.85, and 9.89 at 1, 5, and 10 minutes, respectively. In multiple gestations, the mean birth weight was 2,556.45 g, and the mean Apgar scores were 8.90, 9.34, and 9.47 at 1, 5, and 10 minutes, respectively. Only seven congenital malformations were observed among the 494 babies. Compared with fresh cleavage-stage ETs, the mean birth weight in the vitrified group was higher in both singleton and multiple gestations. All the other results were similar between the two groups. Conclusion(s) Compared with fresh ETs, vitrified day 3 ET shows no significant differences in obstetrical and neonatal outcomes. The study suggests that vitrification with Cryotop is an effective and safe method for the cryopreservation of human cleavage-stage (day 3) embryos.

The aim of this study was to evaluate the safety of laser-assisted hatching (LAH) by comparing obstetric and neonatal outcomes between assisted hatching and control groups in cryopreserved embryo transfer cycles. A retrospective cohort analysis was carried out. A total of 699 women with 392 infants delivered were included. Laser- assisted hatching was carried out on D-3 thawed and warmed embryos before transfer in 480 cryopreserved embryos transfer cycles. Obstetric outcomes, neonatal outcomes, and congenital birth defects were recorded. A total of 815 cryopreserved embryo transfer cycles (480 in LAH group and 335 in control group) in 699 patients were analysed. Statistically significantly higher implantation (31.85% versus 16.95%), clinical pregnancy (53.96% versus 33.43%) and live delivery (44.58% versus 23.88%) rates were observed in the LAH group (all P < 0.001). For either singleton or multiple gestations, no statistically significant differences were found in mean gestational age, mean birth weight and mean Apgar score. Four major malformations occurred in the assisted hatching group and three malformations (one major and two minor) in the control group. This study did not identify any harmful effect of LAH on neonates, which suggested that LAH may be a safe treatment in cryopreserved embryo transfer cycles.