IGFBP7 enhances trophoblast invasion via IGF-1R/c-Jun signaling in unexplained recurrent spontaneous abortion.

In brief: Insufficient trophoblast invasion at the maternal-fetal interface contributes to abortion-prone pregnancy. Our study shows that decreased levels of IGFBP7 in unexplained recurrent spontaneous abortion (URSA) trophoblast cells inhibit MMP2 and Slug expression as well as trophoblast invasion, suggesting that IGFBP7 should be considered a potential therapeutic protein target in URSA. Abstract: Insufficient trophoblast invasion at the maternal-fetal interface contributes to abortion-prone pregnancy. Cyclosporine A (CsA) can exert therapeutic effects on URSA by promoting trophoblast invasion. A previous study showed decreased expression of insulin-like growth factor-binding protein 7 (IGFBP7) in the sera of recurrent spontaneous abortion patients. However, the role of IGFBP7 in URSA remains unknown. The aim of this study was to determine whether IGFBP7 modulates trophoblast invasion in URSA and the underlying molecular mechanisms. We found that IGFBP7 was expressed at lower levels in villous specimens from URSA patients. Manipulating IGFBP7 expression significantly affected the MMP2 and Slug expression in HTR-8/SVneo cells as well as trophoblast invasion in vitro. Inactivation of IGF-1R by IGFBP7 was observed, and IGF-1R inhibition increased the IGFBP7-induced MMP2 and Slug expression in HTR-8/SVneo cells. Moreover, the level of c-Jun was significantly upregulated in the URSA group. Silencing IGFBP7 increased the binding of downstream c-Jun to the MMP2 and Slug promoter regions in HTR-8/SVneo cells, thus suppressing transcription. In addition, increased expression of IGFBP7 in HTR-8/SVneo cells was observed upon CsA treatment. Knockdown of IGFBP7 inhibited the CsA-enhanced MMP2 and Slug expression in HTR-8/SVneo cells. Our results suggest that in normal pregnancy, IGFBP7 induces MMP2 and Slug expression via the IGF-1R-mediated c-Jun signaling pathway, thereby promoting trophoblast invasion. IGFBP7 depletion in URSA inhibits MMP2 and Slug expression as well as trophoblast invasion. Moreover, IGFBP7 participates in CsA-induced trophoblast invasion, suggesting that IGFBP7 is a potential therapeutic target for URSA.

Effect of a carbohydrate-rich beverage on rate of cesarean delivery in primigravidae with epidural labor analgesia: a multicenter randomized trial.

BACKGROUND: Labor represents a period of significant physical activity. Inefficient energy supply may delay labor process and even lead to cesarean delivery. Herein we investigated whether ingestion of a carbohydrate-rich beverage could reduce cesarean delivery in laboring women with epidural analgesia. METHODS: This multicenter randomized trial was conducted in obstetrician-led maternity units of nine tertiary hospitals in China. Primigravidae with single term cephalic pregnancy who were preparing for vaginal birth under epidural analgesia were randomized to intake a carbohydrate-rich beverage or commercially available low-carbohydrate beverages during labor. The primary outcome was the rate of cesarean delivery. Secondary outcomes included maternal feeling of hunger, assessed with an 11-point scale where 0 indicated no hunger and 10 the most severe hunger, and maternal and neonatal blood glucose after childbirth. RESULTS: Between 17 January 2018 and 20 July 2018, 2008 women were enrolled and randomized, 1953 were included in the intention-to-treat analysis. The rate of cesarean delivery did not differ between the two groups (11.3% [111/982] with carbohydrate-rich beverage vs. 10.9% [106/971] with low-carbohydrate beverages; relative risk 1.04, 95% CI 0.81 to 1.33; p = 0.79). Women in the carbohydrate-rich beverage group had lower subjective hunger score (median 3 [interquartile range 2 to 5] vs. 4 [2 to 6]; median difference - 1; 95% CI - 1 to 0; p < 0.01); their neonates had less hypoglycemia (1.0% [10/968] vs. 2.3% [22/956]; relative risk 0.45; 95% CI 0.21 to 0.94; p = 0.03) when compared with those in the low-carbohydrate beverage group. They also had higher rates of maternal hyperglycemia (6.9% [67/965] vs. 1.9% [18/953]; p < 0.01) and neonatal hyperglycemia (9.2% [89/968] vs. 5.8% [55/956]; p < 0.01), but none required special treatment. CONCLUSIONS: For laboring primigravidae with epidural analgesia, ingestion of a carbohydrate-rich beverage compared with low-carbohydrate beverages did not reduce cesarean delivery, but relieved maternal hunger and reduced neonatal hypoglycemia at the expense of increased hyperglycemia of both mothers and neonates. Optimal rate of carbohydrate supplementation remains to be determined. TRIAL REGISTRATION: www.chictr.org.cn ; identifier: ChiCTR-IOR-17011994 ; registered on 14 July 2017.

The association of the glucokinase rs4607517 polymorphism with gestational diabetes mellitus and its interaction with sweets consumption in Chinese women.

OBJECTIVE: To identify the association of the glucokinase gene (GCK) rs4607517 polymorphism with gestational diabetes mellitus (GDM) and determine whether sweets consumption could interact with the polymorphism on GDM in Chinese women. DESIGN: We conducted a case-control study at a hospital including 1015 participants (562 GDM cases and 453 controls). We collected the data of pre-pregnancy BMI, sweets consumption and performed genotyping of the GCK rs4607517 polymorphism. Logistic regression was performed to test the association between the rs4607517 polymorphism and GDM, and the stratified analyses by sweets consumption were conducted, using an additive genetic model. SETTING: A case-control study of women at a hospital in Beijing, China. PARTICIPANTS: One thousand and fifteen Chinese women. RESULTS: The GCK rs4607517 A allele was significantly associated with GDM (OR 1·35, 95 % CI 1·03, 1·77; P = 0·028). Furthermore, stratified analyses showed that the A allele increased the risk of GDM only in women who had a habitual consumption of sweet foods (sweets consumption ≥ once per week) (OR 1·61, 95 % CI 1·17, 2·21; P = 0·003). Significant interaction on GDM was found between the rs4607517 A allele and sweets consumption (P = 0·004). CONCLUSIONS: This study for the first time reported the interaction between the GCK rs4607517 polymorphism and sweets consumption on GDM. The results provided novel evidence for risk assessment and personalised prevention of GDM.

Association of adiposity with thyroid nodules: a cross-sectional study of a healthy population in Beijing, China.

BACKGROUND: The relationship between thyroid nodules (TNs) and adiposity is controversial. This paper describes a cross-sectional investigation performed to determine the existence of any such relationship. To assess adiposity, body mass index (BMI) and visceral fat area (VFA) were utilized. METHODS: Between January 1, 2017 and March 3, 2019. Three thousand five hundred thirty four healthy people were examined using thyroid ultrasonography, visceral fat and anthropometric measurements, laboratory tests and questionnaire interview. Binary logistic regression analyses were used. RESULTS: Of the 3534 healthy subjects, 58.69% (2074/3534) of the subjects had TNs. A total of 55.91% (1976/3534) had BMI ≥ 25 kg/m2 and 39.67% (1402/3534) had VFA ≥ 100 cm2. After adjustment to address confounders, BMI-based overweight and obesity levels only correlated with higher risk TNs when used as a continuous variable (OR = 1.031, 95% CI: 1.008-1.055, P = 0.008), while VFA was both a continuous variable (OR = 1.003, 95% CI: 1.000-1.005, P = 0.034) and a categorical variable (OR = 1.198, 95% CI: 1.014-1.417, P = 0.034) associated with significantly elevated risk of TNs. Analyzing the subgroups, BMI ≥ 25 kg/m2 (OR = 1.500, 95% CI: 1.110-2.026, P = 0.008) was significantly correlated with TN risk in individuals with TG ≥ 1.7 mmol/L. VFA ≥ 100 cm2 correlated with the TN risk irrespective of age (< 50 years: OR = 1.374, 95% CI: 1.109-1.703, P = 0.004; ≥ 50 years: OR = 1.367, 95% CI: 1.063-1.759, P = 0.015) and in the following subgroups: women (OR = 4.575, 95% CI: 2.558-8.181, P = 0.000), FBG ≥ 6.1 mmol/L (OR = 1.522, 95% CI: 1.048-2.209, P = 0.027), and TG ≥ 1.7 mmol/L (OR = 1.414, 95% CI: 1.088-1.838, P = 0.010). CONCLUSIONS: Adiposity correlates with TNs. To assess TN risk in Chinese individuals, VFA is better than BMI.

[Testicular histology does not affect the clinical outcomes of ICSI in men with non-obstructive azoospermia].

OBJECTIVE: To investigate whether testicular histology influences the clinical outcomes of intracytoplasmic sperm injection (ICSI) in men with non-obstructive azoospermia (NOA). METHODS: We retrospectively analyzed the clinical data about 73 cases of NOA undergoing ICSI, including 105 ICSI cycles and 79 embryo transfer cycles. The infertility of the patients was attributed to male factors only or both male and female tube factors and the females' age was ≤38 years. Based on testicular histology, we divided the ICSI cycles into three groups: hypospermatogenesis (HS, n = 72), maturation arrest (MA, n = 21) and Sertoli cells only (SCO, n = 12). We recorded and analyzed the age of both the males and females, infertility duration, base follicle-stimulating hormone (FSH) level, dose and days of gonadotropin (Gn) administration, estradiol (E2) and progesterone (P) levels on the day of human chorionic gonadotropin (hCG) administration, endometrial thickness, number of metaphase II (MII) oocytes, and rates of fertilization, transferrable embryos, high-quality embryos, clinical pregnancy, and abortion. RESULTS: The rates of fertilization, failed fertilization, transferrable embryos, and high-quality embryos, and the average number of transferred embryos were 67.03% (553/825), 9.52% (10/105), 85.66% (472/551), 35.03% (193/551), and 2.10, respectively, resulting in 44 pregnancies (55.70%) and 42 live births (53.16%), with no birth defects. No statistically significant differences were observed among the HS, MA and SCO groups in the mean age of the men and women, infertility duration, base FSH level, Gn dose, Gn days, E2 and P levels on the hCG day, endometrial thickness, or number of MII oocytes, nor in the rates of fertilization (68.51% vs 64.39% vs 61.45%), transferrable embryos (85.05% vs 90.48% vs 83.05%), or high-quality embryos (33.09% vs 41.67% vs 38.98%). The rates of clinical pregnancy and embryo implantation were higher in the HS (60.00% and 37.61%) and SCO (62.50% and 50.00%) than in the MA group (37.50% and 21.21%), but with no statistically significant differences (P >0.05). CONCLUSIONS: Once testicular sperm is retrieved, desirable clinical outcomes can be achieved in ICSI for NOA patients, which is not affected by testicular histopathology.

[Effect of Y chromosomal length variation on male reproductive dysfunction].

OBJECTIVE: To investigate the effects of big and bit Y chromosome configurations on male fertility and to evaluate the relevant clinical significance. METHODS: The relevant cases were divided into A and B groups. Group A included male infertile cases. Group B included cases whose wives had adverse pregnancy history or the abnormal amniotic fluid punctures. The cytogenetics of the patients were examined by culturing peripheral-blood lymphocytes and G-banding technology, and karyotyping analysis techniques were used to study the big and bit Y chromosomes in the two different groups. RESULTS: Among 2 139 cases, 98 cases were found with abnormal karyotype of big and bit Y chromosomes. There was no significant difference in the abnormal rate of the length variation of the Y chromosomal karyotypes between the male infertility group and the adverse pregnancy outcome group. In the male infertile group (group A), there was no significant difference in the abnormal rate between the big Y chromosome and the bit Y chromosome. In the group with adverse pregnancy outcomes (group B), the abnormal rate of the big Y chromosome karyotyping was significantly higher than that of the bit Y chromosome karyotyping. The main clinical effects of groups A and B were azoospermia, oligozoospermia, poor spermia, abortion, embryonic diapause and fetal anomalies, etc . CONCLUSION: The big and bit Y chromosomal abnormality results in not only the male infertility directly, but also an important and continuous reason of adverse pregnancy outcomes, of which the detailed mechanism needs to be further investigated.

[Analysis of obstetric outcomes for different types of placenta previa].

OBJECTIVE: To explore the maternal and perinatal outcomes for different types of placenta previa (PP). METHODS: A total of 343 pregnancies with PP from January 2003 to December 2012 at our hospital were retrospectively reviewed. The general profiles, maternal and perinatal outcomes of different types of 325 singleton PP were evaluated. RESULTS: Among them, 221 pregnancies were of complete PP. There were partial (n = 22) and marginal (n = 82) PP. Proportions of previous vaginal and cesarean deliveries in women with complete and partial PP were higher than those with marginal PP (P < 0.05). Compared with marginal PP group, ratio of placenta in the uterus posterior wall prepartum hemorrhage and probability of blood transfusion and neonatal asphyxia were much higher in complete and partial PP. The gestational age at delivery and neonatal body weight with complete PP and partial PP marginal PP were higher than those of the other two groups (P < 0.05). As for the placenta adhesion, placenta accrete or postpartum hemorrhage, no difference existed among three groups placenta location. CONCLUSION: The gestational age at delivery, prepartum hemorrhage, probability of blood transfusion and perinatal outcome in women with PP are related with the type of PP. Both complete and partial PP have relatively worse outcomes. The type of PP has no effect on placenta adhesion, placenta accrete or postpartum hemorrhage.

[Long-term effects of mild hyperglycemia exposure in utero and postnatal high fat diet on body weight and lipid metabolism in rat offsprings].

OBJECTIVE: To investigate the long-term effects of intrauterine mild hyperglycemia exposure and postnatal high fat diet on the body weight and metabolism of offspring through a pregnant rat model of intrauterine mild hyperglycemia. METHODS: Twenty-one pregnant Wistar rats were randomly divided into intrauterine hyperglycemia group and control group. Twenty percent streptozotocin (STZ, 25 mg/kg)was given to rats of intrauterine hyperglycemia group by a single intraperitoneal injection to induce intrauterine mild hyperglycemia; control group rats received an equal volume of citric acid-sodium citrate buffer. Off springs were divided into 4 groups: exposed to intrauterine hyperglycemia and fed with normal diet group (group DN) or high fat diet group (group DF); exposed to intrauterine euglycemia and fed with normal diet group (group CN) or high fat diet group (group CF). The blood glucose levels of pregnant rats in two groups and body weights of offsprings in four groups were recorded. At the age of 28 weeks, the mesenteric fat amount, epididymal amount, perirenal fat amount, total triglyceride (TG) and high density 1ipoprotein-cholestrol (HDL-C) were measured in all four groups. RESULTS: (1)The average blood glucose level of intrauterine hyperglycemia group [(16.6 ± 3.4) mmol/L] was significantly higher than that of the control group [(5.8 ± 1.1) mmol/L, P < 0.01]. (2) On the birth day, 3 weeks and 4 weeks, the body weight of group DN[(7.4 ± 0.6), (44.1 ± 5.9), (79.6 ± 7.4) g] and group DF [(7.4 ± 0.2), (43.9 ± 6.9), (76.1 ± 5.8) g] were remarkably increased compared with group CN [(6.6 ± 0.5),(35.6 ± 4.4),(71.5 ± 6.8) g, P < 0.05]; but the body weight in group CF [(6.7 ± 0.5),(33.0 ± 6.5),(66.1 ± 10.2) g] had no statistical difference compared with group CN (P > 0.05). (3)From then on, the body weights of the offsprings in four groups presented an increasing trend, but there was no statistical difference until 28 weeks (P > 0.05). (4) The perirenal fat amount of group DN, group CF and group DF [(13.8 ± 3.3), (14.3 ± 3.2), (18.4 ± 1.3) g] were remarkably increased compared with group CN[(9.7 ± 3.5) g, P < 0.05]; the epididymal fat amount of group CF and group DF were also significantly increased compared to group CN (P < 0.05); the mesenteric fat amount in four groups had no statistical difference (P > 0.05). (5) The TG level of group DN, group CF and group DF [(0.52 ± 0.14), (0.52 ± 0.09), (0.54 ± 0.17) mmol/L] were significantly higher compared to group CN [(0.41 ± 0.09) mmol/L, P < 0.05], but there was no statistical difference within the first three groups (P > 0.05); the HDL-C level in four groups had no statistical difference (P > 0.05). CONCLUSIONS: In intrauterine mild hyperglycemia environment, there were some evidently metabolic changes observed in the offspring, including body weight increasing on birth day and early postnatal period, visceral fat amount increasing and lipid metabolism disorders, which could be aggravated by postnatal high fat diet.

[Initial research of serum glycated albumin during pregnancy].

OBJECTIVE: To explore the normal range of serum glycated albumin (GA) during the second trimester in non-gestational diabetes mellitus (GDM) population and the value of serum GA in the blood glucose monitoring during pregnancy. METHODS: The GA was measured in 101 healthy gravida during the second trimester and 80 gravida with GDM and diabetes mellitus who were in treatment at Peking University First Hospital between August 2011 and December 2011, in order to analyze the normal range of GA and the relationship between GA and the level of blood glucose. RESULTS: (1) The normal range of GA during the second trimester was 10.9%-15.3%, which was negatively correlated with body mass index (P < 0.01). (2) Significant correlations were observed between GA and the level of hemoglobin A1c (HbA1c), preprandial, postprandial and mean plasma glucose in gravida with GDM and diabetes mellitus (r:0.361, 0.252, 0.338, 0.310;all P < 0.05). (3) When the level of GA was 13.97%, the sensitivity and specificity index for glucose control were 78.0% and 74.4%. CONCLUSIONS: GA could evaluate the severity of disease in gravida with GDM and diabetes mellitus. 10.9%-15.3% could be suggested as normal range of GA for the gravida at the second trimester.

[Analysis of the effects of gestational diabetes mellitus based on abnormal blood glucose on pregnancy outcomes].

OBJECTIVE: To investigate the relationship of different types of gestational diabetes mellitus (GDM) and pregnancy outcomes. METHODS: A total of 4090 cases, who received prenatal examination and delivered in Peking University First Hospital and performed a 75 g oral glucose tolerance test (75 g OGTT) at 24-28 gestational weeks, from January. 1(st), 2011 to Jul 31(st), 2012 , were divided into 2 groups. Normal blood glucose group:the result of OGTT (fasting plasma glucose, 1 hour glucose and 2 hour glucose ) was normal; Gestational diabetes mellitus group (GDM group): the result of OGTT was abnormal at any time point. GDM group were separated into A, B and C. GDM A means fasting plasma glucose annormal but others were normal, GDM B:fasting plasma glucose, 1 hour and/or 2 hour glucose abnormal, GDM C:fasting plasma glucose normal. To analyse the effect of different number of abnormal result of OGTT on pregnancy outcomes, GDM group were divided into I, II and III.GDMI means one abnormal blood glucose of OGTT result, GDM II: two abnormal blood glucose and GDM III:three abnormal blood glucose. We analyzed the pregnant outcomes of each group. RESULTS: (1) Among the 4090 cases, 858 cases (21.98%) were diagnosed as GDM (GDM group), and 82 cases (9.6%, 82/858) were treated with insulin.other 3232 cases with normal blood glucose (normal blood glucose group). In GDM group, the rate of cesarean section (51.9%, 445/858), premature delivery (8.4%, 72/858) and LGA (5.9%, 51/858) were respectively significantly higher than those of normal blood glucose group [ (43.5%, 1406/3232), (5.8%, 189/3232) and(4.2%, 137/3232)] (P < 0.05). But, there was no statistically significant differences for the rate of macrosomia (P > 0.05) between the GDM group(6.8%, 58/858) and normal blood glucose group (6.2%, 199/3232) . (2) In the GDM group, GDM A was 317 cases (36.9%), GDM B 239 cases (27.8%), GDM C 302 cases (35.2%). The incidence of Macrosomia and LGA in GDM B was significantly higher than that in GDM C and normal blood glucose group (P < 0.05). Comparing with GDM A , there was no statistically significance in GDM B and GDM C (P > 0.05). (3) In GDM group, GDMIwas 521 cases (60.7%), GDM II203 cases (15.6%), GDM III 134 cases (23.7%). Compared with the normal blood glucose group, GDM III had a significantly higher incidence of macrosomia and LGA and cesarean section(P < 0.01);and GDM IIhad only a significantly higher incidence of cesarean section(P < 0.01). (4) Among the 4090 cases, there were 1118 patients (27.3%) whose fasting blood glucose was below 4.4 mmol/L, of which 55 cases were diagnosed as GDM. There were 4 premature infants and 1 macrosomia. CONCLUSIONS: The GDM group with more than FBG ≥ 5.1 mmol/L had a higher incidence of adverse pregnancy outcomes, it suggested that we should pay more attention and take actively intervented; the pregnant woman is not recommended for 75g OGTT detection when fasting blood glucose was below 4.4 mmol/L because of the low rate of GDM and adverse pregnancy outcomes among them.

[Study on mode of delivery and singleton newborns term birth weight in 3 hospitals].

OBJECTIVE: To study newborns weight in singleton term births and the association between newborns birth weight and mode of delivery in 3 hospitals. METHODS: From Jan. 2005 to Dec. 2009, 13 963 singleton term live neonates born in the Department of Obstetrics and Gynecology of Peking University First Hospital (PU group), 6519 neonates in Affiliated Hospital of Binzhou Medical College (BMC group,) and 8725 neonates in Miyun Hospital Affiliated to Capital Medical University, Yanjing Medical College (MYC group) were enrolled in this retrospective study. The newborns weight and the rate of macrosomia was calculated and compared. Those newborns from PU group and MYC group were divided into 2288 neonates at macrosomia group and 20 400 neonates at non-macrosomia group, their mode of deliveries were analyzed. RESULTS: (1) The mean neonatal birth weight were (3386 ± 414) g at PU group, (3389 ± 446) g at BMC group and (3445 ± 449) g at MYC group. Neonates born weight in MYC was significantly higher than those from in PU group and BMC group (P = 0.000). Neonates born weight in BMC showed higher than those in PU group, which did not reached statistical difference (P = 0.638). (2) The incidence of macrosomia were 7.935% (1108/13 963) in PU group, 9.802% (639/6519) in BMU group and 13.524% (1180/8725) in MYU group. The incidence of macrosomia in MYC group was higher than those in PU and BMC group, the incidence of macrosomia in BMC group was higher than that in PU group, which reached statistically difference (P = 0.000). (3)The proportion of cesarean delivery were 75.306% (1723/2288) at macrosomia group, 50.765% (10 356/20 400) at non-macrosomia group, which showed statistical difference (P = 0.000). CONCLUSIONS: (1) The difference of newborns birth weight existed in different administrative level hospital. (2) The risk of cesarean delivery due to macrosomia is higher than that of non-macrosomia. (3) Obstetricians should pay more attention to nutrition in gestation period to lessen the incidence of macrosomia and cesarean section.

Neonatal hyperinsulinism with an ABCC8 mutation: A case report.

BACKGROUND: Neonatal hyperinsulinism can result from perinatal stress, genetic disorders, or syndromes, which can lead to persistent or intractable hypoglycemia in newborns. Mutations in the ABCC8 gene result in abnormal functioning of potassium channel proteins in pancreatic ß-cells, leading to an overproduction of insulin and congenital hyperinsulinemia. CASE SUMMARY: We report a case of a high-birth-weight infant with postnatal hypoglycemia and hyperinsulinemia, whose mother had pregestational diabetes mellitus with poor glycemic control and whose sister had a similar history at birth. Whole-exome sequencing revealed a new mutation in the ABCC8 gene in exon 8 (c.1257T>G), which also occurred in his sister and mother; thus, the patient was diagnosed with neonatal hyperinsulinism with an ABCC8 mutation. With oral diazoxide treatment, the child's blood glucose returned to normal, and the pediatrician gradually discontinued treatment because of the child's good growth and development. CONCLUSION: We report a new mutation locus in the ABCC8 gene. This mutation locus warrants attention for genetic disorders and long-term prognoses of hypoglycemic children.

Visualization of Confined Electrons at Grain Boundaries in a Monolayer Charge-Density-Wave Metal.

1D grain boundaries in transition metal dichalcogenides (TMDs) are ideal for investigating the collective electron behavior in confined systems. However, clear identification of atomic structures at the grain boundaries, as well as precise characterization of the electronic ground states, have largely been elusive. Here, direct evidence for the confined electronic states and the charge density modulations at mirror twin boundaries (MTBs) of monolayer NbSe2 , a representative charge-density-wave (CDW) metal, is provided. The scanning tunneling microscopy (STM) measurements, accompanied by the first-principles calculations, reveal that there are two types of MTBs in monolayer NbSe2 , both of which exhibit band bending effect and 1D boundary states. Moreover, the intrinsic CDW signatures of monolayer NbSe2 are dramatically suppressed as approaching an isolated MTB but can be either enhanced or suppressed in the MTB-constituted confined wedges. Such a phenomenon can be well explained by the MTB-CDW interference interactions. The results reveal the underlying physics of the confined electrons at MTBs of CDW metals, paving the way for the grain boundary engineering of the functionality.

[Effect of Ras signal regulating Cox7a2 expression and its sub-cellular location in testicular interstitial cell].

OBJECTIVE: To investigate the co-sub-cellular-location of Cox7a2 and Ras. METHODS: Ras and its mutant plasmid were cloned by RT-PCR and sequence analysis. Cox7a2-pEYFP-N1, Ras-pEYFP-N1 and N17-Ras-pEYFP-N1 fluorescent protein vectors were constructed and transfected into TM3 cells. RESULTS: Cox7a2 was located in the mitochondria, but its location was changed by the expression of Ras. When the dominant negative ras was expressed in the cells, the Cox7a2 located into the mitochondria again. CONCLUSION: Cox7a2 mediated testosterone production, which might be at least in part related with the Ras signaling pathway. Ras may be the regulating target and further investigation is needed to make it clear.

[Investigation into the clinical suitability of Institute of Medicine 2009 guidelines regarding weight gain during pregnancy for women with full term singleton fetus in China].

OBJECTIVE: To study whether the current Institute of Medicine (IOM) pregnancy weight gain recommendations vary by pre-pregnancy body mass index (BMI) was suitable to Chinese people. METHODS: A study was conducted on 4736 term singleton live birth gravidas, who were diagnosed normal glucose metabolism and delivered in Peking University First Hospital in 2005 and 2009, by reviewing the medical records. Based on the pre-pregnant BMI, the selected cases were divided into 3 groups: low body mass group (BMI < 18.5 kg/m(2), n = 465), normal body mass group (BMI 18.5 - 24.9 kg/m(2), n = 3549), over body mass group (BMI ≥ 25 kg/m(2), n = 722). All the cases were divided into 3 subgroups based on pregnancy weight gain as below, within, and above the IOM recommendations in each pre-pregnant BMI group. Totally 4736 newborns were divided by birth weight into 3 groups: normal birth weight group (weight 2500 - 4000 g, n = 4339), macrosomia group (weight ≥ 4000 g, n = 359) and low birth weight group (weight < 2500 g, n = 38). The difference of age, gestational age, pre-pregnant weight, pre-pregnant BMI and history of delivery of cases between 2005 and 2009 were analyzed. The difference of pregnancy outcome of women whose gestational weight gain was below, within, and above the IOM recommendations was analyzed. RESULTS: (1) Compared to mothers with pregnancy weight gain within IOM recommendations in low body mass group, risk of low birth weight in offspring was elevated tendency with pregnancy weight gain below IOM recommendations (OR = 3.71, 95%CI: 0.97 - 14.12, P = 0.055). (2) In normal body mass group, compared to women with pregnancy weight gain within IOM recommendations, risk of macrosomia in offspring was elevated with pregnancy weight gain above IOM recommendations (OR = 2.14, 95%CI: 1.62 - 2.83, P < 0.01). (3) In over body mass group, compared to women with pregnancy weight gain within IOM recommendations, risk of macrosomia in offspring was elevated (OR = 3.25, 95%CI: 1.65 - 6.39, P = 0.001) and risk of hypertensive disorders complicating pregnancy was high (OR = 1.79, 95%CI: 1.04 - 3.09, P = 0.037) in women with pregnancy weight gain above IOM recommendations. CONCLUSION: The current IOM pregnancy weight gain recommendations vary by pre-pregnancy BMI may be suitable to Chinese people.

[Roles of advanced glycation end products and its receptor on the fetal brain injury in pregnant rats with gestational diabetes mellitus].

OBJECTIVE: To study the roles of advanced glycation end products and its receptor on fetal brain injury of gestational diabetes mellitus (GDM) rats. METHODS: Twenty one adult pregnant Wistar rats were administered streptozotocin (STZ) intraperitoneally to induce GDM rats model. The fourteen pregnant rats were divided into two groups according to the fasting glucose on the 3(rd) day of pregnancy:severe GDM group with the fasting glucose > 16.7 mmol/L and mild GDM group with the fasting glucose between 6.7 - 16.7 mmol/L. Another seven pregnant rats were chosen as the severe GDM and intervention with micronutrient group, receiving gavage with micronutrient during the whole pregnancy. Five control rats received the same volume of citric acid buffer. All the pregnant rats were tested fasting glucose from the tail vein and their weight on the pregnant day 3, 13 and 19. Maternal serum levels of AGE were measured by ELISA and RAGE levels in the embryonic brain tissues were tested by immunohistochemistry. RESULTS: (1) There was no statistically significant difference of pre-pregnancy fasting glucose level among all groups (P > 0.05). The fasting glucose levels on the 3(rd) day and the mean fasting glucouse level of pregnancy in the severe GDM group and the severe GDM and intervention with micronutrient group were higher than those of the control group (P < 0.05). And there was no significant difference between the severe GDM group and the severe GDM and intervention with micronutrient group (P > 0.05). (2) The serum AGE levels in the severe GDM group and the mild GDM group were (1037 ± 38) ng/L and (880 ± 34) ng/L respectively, with no significant difference (P > 0.05). The serum AGE levels in the control group and the severe GDM and intervention with micronutrient group were (857 ± 32) ng/L and (988 ± 37) ng/L, and the difference was statistically significant (P < 0.05). The serum AGE levels in the severe GDM and intervention with micronutrient group and in the mild GDM group had no significant difference (P > 0.05). (3) The serum AGE levels in the severe GDM group, mild GDM group and the control group were positively associated with the mean glucose level of pregnancy (r = 0.603, P < 0.05) and the grlucose on the 3(rd) day of pregnancy (r = 0.704, P < 0.05). (4) The fetal brain nerve cell number and morphology in the control group were normal. While in the mild GDM group fetal brain nerve cells decreased, the proliferation and swelling of glial cells were seen. In the severe GDM group and the severe GDM and intervention with micronutrient group, the fetal brain cells furtherly reduced, and large vacuole around the cells, deformation and debris of the cells were seen. Glial scar formation was visible in some fetal brain tissues. There was a few RAGE expression in the control fetal brain tissues. In the mild GDM group and the severe GDM group, RAGE expression increased significantly. And the RAGE expression intensity in the severe GDM and intervention with micronutrient group was between the severe and the mild GDM groups. CONCLUSIONS: (1) Abnormal fetal brain development of GDM rats was associated with the increase of maternal serum AGE and the enhancement of RAGE expression in fetal brain tissues, which suggested that AGE/RAGE pathway may play an important role in the fetal brain injury of GDM rats. (2) Micronutrients can reduce the brain damage of GDM fetuses.

[Streptozotocin-induced maternal intrauterine hyperglycemia environment and its influence on development and metabolic in adult offspring with high birth weight in rats].

OBJECTIVE: To establish and assess the high-birth-weight offspring model of the diabetic rat induced by stueptozotocin, and the long-term metabolic impact of maternal hyperglycemia of those offsprings. METHODS: Streptozotocin (STZ, 25 mg/kg) was given to Wistar rats (G group, n = 14) once intraperitoneally to induce maternal hyperglycemia model (blood glucose between 10 - 20 mmol/L), and there still had a number of rats defined as severe hyperglycemia model group (SG group, n = 5). The Control group (C group, n = 7) were given the same volume citrate buffer solution. The body weight and blood glucose were recorded, and the lavaging glucose tolerance test (LGTT) was performed by a glucose meter in the gestation. The offsprings were corresponding allocated into 2 groups, and the birth weight were recorded. All the offsprings were observated body weight, blood glucose blood pressure (male rats only), and so on. RESULTS: (1) The blood glucose of G group (16.8 ± 5.4 mmol/L) and SG group (20.5 ± 5.6 mmol/L) were increased significantly as compared with C group (7.0 ± 1.4 mmol/L) 5 days after the model was established (P < 0.01); and the average blood glucose of G group (16.6 ± 3.4 mmol/L) and SG group (23.8 ± 1.5 mmol/L) increased too as comparede with C group (5.8 ± 1.1 mmol/L), the difference was significance according to statistics (P < 0.01). (2) According to the LGTT result, which operationed on generation day 4 and day 10, the blood glucose of every time point of G group were increased significantly as compared with C group (P < 0.01). (3) The male and female birth weight of G group was remarkably higher than the C group and the SG group (P < 0.05), and the blood glucose of SG/G/C group was (6.5 ± 1.2) mmol/L, (4.1 ± 0.8) mmol/L, (4.1 ± 0.8) mmol/L respectively, according to the statistics results, the difference between SG group and G/C group respectively both remarkable (P < 0.05). (4) The body weight, Lee's index, fat weight, and the fat weight of mass ratio in C group mother rats after lactation presented dressed compared with the SG group (P < 0.05), and so as to the G group compared with the SG group (P < 0.05). (5) In the female offsprings of G group, the birth weight was remarkably increased compared with the C group (P < 0.05); the body weight of the female offsprings presented an increased trend compared with the C group since the 12 weeks, but had no statistical significance; there were significant differences of body weight between G group and C group since 15 weeks (P < 0.05), and the trend kept up until 26 weeks; in the male offsprings of G group, the body weight on birth day and 4 weeks had a marked rise compared with the C group (P < 0.05); and from then on, the body weight of the male offsprings presented an increased trend compared with the C group, but had no statistical significance until 26 weeks (P > 0.05). (6) In G group, the blood glucose on 30 min and 60 min of LGTT in female offsprings were increased than the C group since 20 weeks (P < 0.05); the blood glucose of LGTT (30 min) still had a marked rise until 24 weeks (P < 0.05); in G group, the blood glucose on 30 min of LGTT in male offsprings was remarkably increased than the C group since 16 weeks (P < 0.05) ; the blood glucose of LGTT (30 min) still had a marked rise until 24 weeks (P < 0.05). (7) The blood pressure of male offsprings in G group had a marked rise on 12 weeks compared with the C group (P < 0.05); from then on the blood pressure of G group kept up a rise trend until 26 weeks, but had no statistical significance (P > 0.05). CONCLUSION: The diabetic high-birth-weight rat model could be duplicated with STZ (25 mg/kg) once intrapertoneally on the first day of gestation, which were observed some evidently metabolic changes in weight, glucose tolerance and blood pressure. These results could represent an forward step in the clinical study of human gestational diabetes mellitus and their macrosomia babies, which may suffer some metabolic disease in their later life.

Myomatous erythrocytosis syndrome: A case report.

BACKGROUND: Uterine myoma is the most common benign tumor among women and is often accompanied by anemia. Here, we report the case of a patient with a very large leiomyoma but with a hemoglobin level as high as 197 g/L. After undergoing hysterectomy, all her hematological parameters returned to normal. Immunohistochemical staining of her myoma for erythropoietin showed strong positivity, which suggested that erythropoietin may be the cause of her erythrocytosis. A multidisciplinary team played a significant role in treating the disease. CASE SUMMARY: A 47-year-old woman visited our department complaining that her abdomen had been continuously growing for the past 2 years. After careful examinations, she was suspected of having a very large leiomyoma. She was also diagnosed with erythrocytosis because her RBC count was 6.49 × 1012/L, hemoglobin was 197 g/L. Following a multidisciplinary team consultation, bilateral ureteral stents were placed, and 800 mL blood was removed by phlebotomy. The patient then underwent hysterectomy and bilateral salpingectomy. She recovered well from the operation, and her hemoglobin level decreased sharply following the surgery. Low-molecular-weight heparin was administered daily to prevent postoperative thrombosis. She was discharged from the hospital on the fourth postoperative day. Two months later, all her hematological parameters returned to normal. Pathological analysis of the myoma revealed that it was a benign leiomyoma, with partial hyalinization, and strong positivity for erythropoietin in immunohistochemical staining suggested that erythropoietin may be responsible for the erythrocytosis. CONCLUSION: Erythropoietin ectopically produced from the myoma was responsible for the erythrocytosis in this patient. A multidisciplinary team is strongly recommended.

Endometrial squamous cell carcinoma originating from the cervix: A case report.

BACKGROUND: Cervical squamous cell carcinoma (SCC) is the most common type of cervical carcinoma and is generally derived from a precancerous stage called cervical high-grade squamous intraepithelial lesion (HSIL). Usually, the cancer metastasizes through lymphatic or hematogenous dissemination, but rarely spreads upward into the uterus. Here, we report a case of cervical HSIL extending into the endometrium and finally progressing to SCC in the uterine cavity. CASE SUMMARY: A 57-year-old postmenopausal woman visited our department and requested a routine cervical check-up. Four years ago, she had undergone a cervical loop electrosurgical excision procedure because of HSIL found during the gynecological examination, and she had not been checked again since. This time, a relapse of the cervical HSIL was diagnosed along with uterine pyometra and endometrial polyps. After 2 wk of antibiotic treatment, a laparoscopic hysterectomy was performed, and the final pathological examination revealed that the cervical HSIL had spread directly upward into the uterine cavity, gradually developing into cervical SCC in the endometrium. CONCLUSION: Cervical HSIL/SCC can directly spread upward into the uterus with the most common symptoms of pyometra and cervical stenosis. More attention should be given to the early detection and prevention of this disease.