Fetal overgrowth and weight trajectories during infancy and adiposity in early childhood.

BACKGROUND: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood. Little is known about how infancy growth trajectories affect adiposity in early childhood in LGA. METHODS: In the Shanghai Birth Cohort, we followed up 259 LGA (birth weight >90th percentile) and 1673 appropriate-for-gestational age (AGA, 10th-90th percentiles) children on body composition (by InBody 770) at age 4 years. Adiposity outcomes include body fat mass (BFM), percent body fat (PBF), body mass index (BMI), overweight/obesity, and high adiposity (PBF >85th percentile). RESULTS: Three weight growth trajectories (low, mid, and high) during infancy (0-2 years) were identified in AGA and LGA subjects separately. BFM, PBF and BMI were progressively higher from low- to mid-to high-growth trajectories in both AGA and LGA children. Compared to the mid-growth trajectory, the high-growth trajectory was associated with greater increases in BFM and the odds of overweight/obesity or high adiposity in LGA than in AGA children (tests for interactions, all P < 0.05). CONCLUSIONS: Weight trajectories during infancy affect adiposity in early childhood regardless of LGA or not. The study is the first to demonstrate that high-growth weight trajectory during infancy has a greater impact on adiposity in early childhood in LGA than in AGA subjects. IMPACT: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood, but little is known about how weight trajectories during infancy affect adiposity during early childhood in LGA subjects. The study is the first to demonstrate a greater impact of high-growth weight trajectory during infancy (0-2 years) on adiposity in early childhood (at age 4 years) in subjects with fetal overgrowth (LGA) than in those with normal birth size (appropriate-for-gestational age). Weight trajectory monitoring may be a valuable tool in identifying high-risk LGA children for close follow-ups and interventions to decrease the risk of obesity.

Effects of obesity indices/GDM on the pregnancy outcomes in Chinese women: A retrospective cohort study.

Objective: To analyze pregnancy complications and outcomes of mothers with obesity or gestational diabetes mellitus (GDM). Methods: 15065 mothers were categorized into four and three groups by pre-pregnancy body mass index (preBMI) and abdominal circumference (AC), respectively, or divided into GDM or non-GDM groups. Logistic regression analysis was utilized to identify independent factors associated with pregnancy complications and outcomes. Results: The overweight and obesity groups accounted for 16.0% and 4.0% of the total population, respectively. GDM incidence rate was 12.3%. The overweight and obesity groups (pre-pregnancy body mass index [preBMI] ≥ 24 kg/m2) were at higher risks for GDM, hypertensive disorders of pregnancy (HDP), gestational proteinuria, postpartum hemorrhage, preterm delivery, fetal malformation or stillbirth, neonatal asphyxia, large for gestational age (LGA), shoulder dystocia, and increased cesarean section rate. Similar results were obtained with AC grouping. GDM pregnant women had higher risks of HDP, preterm delivery, small for gestational age (SGA), LGA, and increased cesarean section rate. Conclusion: People with obesity had a higher risk of adverse pregnancy outcomes. The recommended preBMI is 19.2-22.7 kg/m2. The recommended AC at 11-13+6 gestational weeks is 74.0-84.0 cm, and that value in normal preBMI is 74.0-82.0 cm.

Maternal vitamin D status in early pregnancy and its association with gestational diabetes mellitus in Shanghai: a retrospective cohort study.

BACKGROUND: There is growing interest regarding vitamin D and its potential role in gestational diabetes mellitus (GDM). We aimed to assess maternal vitamin D status in early pregnancy and its relationships with the risk of GDM in a Chinese population in Shanghai. METHODS: The retrospective cohort study included a total of 7816 pregnant women who underwent a 75-g oral glucose tolerance test (OGTT) during 24-28 weeks of gestation. Participants' demographic information including maternal age, prepregnancy body mass index (BMI), gestational age, parity, season of blood collection, serum 25-hydroxy vitamin D [25(OH)D] data and other blood biomarker data at 6 to 14 weeks of gestation were retrospectivly extracted from the medical records in the hospital information system. RESULTS: In the cohort, the prevalence of GDM was 8.6% and the prevalence of vitamin D deficiency and insufficiency in early pregnancy was 53.1 and 38.5%, respectively. The mean value of the serum 25(OH)D concentration was 19.6±7.5 ng/mL. The restricted cubic splines model showed an inverted J-shaped relationship in which the risk of GDM decreased when the 25(OH)D concentrations were ≥ 20 ng/mL. Logistic model analysis showed that 25(OH)D concentrations ≥ 30 ng/mL significantly decreased the risk of GDM (odds ratio = 0.63, 95% confidence interval: 0.45-0.89; P = 0.010) compared with 25(OH)D concentrations < 20 ng/ml. CONCLUSIONS: In early pregnancy, vitamin D deficiency and insufficiency were very common, and a high level of vitamin D showed protective effects against the incidence risk of GDM.

Silencing eL31 suppresses the progression of colorectal cancer via targeting DEPDC1.

BACKGROUND: Colorectal cancer (CRC) is one of the most commonly diagnosed human malignancies. Ribosomal protein L31 (RPL31, aka eL31) is a component of the 60S large ribosomal subunit, and its expression pattern and functional role in CRC have not been reported. METHODS: Herein, we identified that eL31 protein level was dramatically increased in CRC tissues through using IHC analysis. More notably, elevated eL31 was associated with larger tumor size and shorter overall survival. Besides, we evaluated the effects of eL31 depletion on CRC cell phenotypes in vitro. RESULTS: The data indicated that eL31 knockdown restricted CRC cell proliferation, migration and colony formation whilst enhancing cell apoptosis. Importantly, eL31 was also essential for CRC tumor growth in vivo, as demonstrated by impaired tumor growth markers and reduced Ki67 levels in xenografts from eL31-depleted cells. In addition, our evidence indicated that DEP domain containing 1 (DEPDC1) was a potential downstream target of eL31 in regulating CRC. Consistently, DEPDC1 depletion restrained CRC cell proliferation and migration, as well as facilitated cell apoptosis. More interestingly, DEPDC1 depletion could reverse the promotion effects of eL31 elevation on CRC cells. CONCLUSIONS: Identification of eL31's function in CRC may pave the way for future development of more specific and more effective targeted therapy strategies against CRC.

M1­like tumor­associated macrophages enhance proliferation and anti­apoptotic ability of liver cancer cells via activating the NF­κB signaling pathway.

Liver cancer is the second leading cause of cancer­associated death worldwide. The present study aimed to evaluate the infiltration of M1­like tumor­associated macrophages (TAMs) and explore the role of infiltration of M1­like TAMs in the proliferation and apoptosis evasion of liver cancer cells. Furthermore, the association between M1­like TAM and the efficacy of postoperative transcatheter arterial chemoembolization (TACE) for patients with liver cancer was investigated. The levels of CD68, human leukocyte antigen­DR and phosphorylated NF­κB (p­)p65 were detected by western blot analysis and immunohistochemistry. Cell cycle analysis, MTT and clonogenic assays were utilized to investigate the proliferation of liver cancer cells. It was indicated that M1­like TAM increased the p­p65/p65 ratio in liver cancer cells and promoted cell proliferation. Furthermore, JSH­23, an inhibitor that prevents p65 from entering the nucleus, decreased the proliferation of liver cancer cells in M1­like TAM­conditioned medium. In addition, M1­like TAM increased the number of liver cancer cells in the S and G2/M phases of the cell cycle and also upregulated the expression levels of cyclin­dependent kinase (CDK)1, CDK2 and cyclin D1. By contrast, M1­like TAM decreased the expression level of p21. Through these effects, the anti­apoptotic ability of liver cancer cells was enhanced. Of note, JSH­23 reversed these changes related to the cell cycle, anti­apoptotic ability and the expression levels of proteins induced by M1­like TAM in liver cancer cells. In conclusion, the infiltration of M1­like TAM in liver tissue negatively influenced the efficacy of postoperative TACE for patients with liver cancer.

Prediction of gestational diabetes mellitus by different obesity indices.

BACKGROUND: The incidence rates of obesity and gestational diabetes mellitus (GDM) are increasing in parallel. This study aimed to evaluate the relationship between different obesity indices, including prepregnancy body mass index (preBMI), the first-trimester abdominal circumference (AC), and first-trimester abdominal circumference/height ratio (ACHtR), and GDM, and the efficacy of these three indices in predicting GDM was assessed. METHODS: A total of 15,472 pregnant women gave birth to a singleton at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. Prepregnancy weight was self-reported by study participants, body height and AC were measured by nurses at the first prenatal visit during weeks 11 to 13+6 of pregnancy. GDM was diagnosed through a 75-g oral glucose tolerance test at 24-28 gestational weeks. Using receiver operator characteristic (ROC) curve analysis, we evaluated the association between obesity indices and GDM. RESULTS: A total of 1912 women (12.4%) were diagnosed with GDM. Logistic regression analysis showed that AC, ACHtR, and preBMI (P < 0.001) were all independent risk factors for the development of GDM. In the normal BMI population, the higher the AC or ACHtR was, the more likely the pregnant woman was to develop GDM. The area under the ROC curve (AUC) was 0.63 (95% CI: 0.62-0.64) for the AC, 0.64 (95% CI: 0.62-0.65) for the ACHtR and 0.63 (95% CI: 0.62-0.64) for the preBMI. An AC ≥ 80.3 cm (sensitivity: 61.6%; specificity: 57.9%), an ACHtR of ≥ 0.49 (sensitivity: 67.3%; specificity: 54.0%), and a preBMI ≥ 22.7 (sensitivity: 48.4%; specificity: 71.8%) were determined to be the best cut-off levels for identifying subjects with GDM. CONCLUSIONS: An increase in ACHtR may be an independent risk factor for GDM in the first trimester of pregnancy. Even in the normal BMI population, the higher the AC and ACHtR are, the more likely a pregnant woman is to develop GDM. AC, ACHtR in the first trimester and preBMI might be anthropometric indices for predicting GDM, but a single obesity index had limited predictive value for GDM.

Progesterone Attenuates SIRT1-Deficiency-Mediated Pre-Eclampsia.

Pre-eclampsia is a severe hypertensive disorder of pregnancy (HDP), mainly characterized by new-onset hypertension with proteinuria after 20-week gestation. Sirtuin1 (SIRT1), a class III histone deacetylase, is associated with the regulation of various pathophysiological processes, including inflammation, immune response, metabolism, and autophagy. However, the effect of SIRT1 in the pathogenesis of pre-eclampsia remains to be elucidated. In this study, we found that the expression of SIRT1 was relatively lower in the placentas and serum samples of pre-eclampsia patients. Typical pre-eclampsia-like symptoms, such as hypertension, proteinuria, fetal growth restriction, kidney injury, and a narrow placental labyrinth layer, were observed in SIRT1 knockdown (SIRT1+/-) mice. Of note, these performances could be improved after the intraperitoneal injection of SIRT1 agonist SRT2104. More importantly, we found that the efficacy of progesterone on attenuating symptoms of PE was profoundly better than that of metformin in SIRT1+/- mice. In addition, our results suggested that progesterone can promote the invasion and inhibit the apoptosis of trophoblasts. These data suggest that SIRT1 plays an important role in pre-eclampsia and that progesterone alleviates pre-eclampsia-like symptoms mediated by SIRT1 deficiency.

LncRNA UCA1 Enhances Cisplatin Resistance by Regulating CYP1B1-mediated Apoptosis via miR-513a-3p in Human Gastric Cancer.

BACKGROUND: Chemoresistance contributes to treatment failure of gastric cancer (GC) patients but the molecular mechanism of chemoresistance in GC is still unclear. Long-chain noncoding RNA (lncRNA) urothelial cancer associated 1 (UCA1) is associated with resistance to chemotherapy drugs. METHODS: We detected the expression of UCA1 in 53 pairs of GC tumor tissue and adjacent normal tissue, human normal gastric mucosa cells (GES-1) and human GC cells (HGC-27, SNU-5, AGS, SGC-7901, and NCI-N87) using RT-qPCR. Small RNA interference technology was used to knock down the expression of UCA1 in gastric cancer cells. CCK8 solution was used to detect cell viability. Flow cytometry was used to detect apoptosis, and Western blotting was used to detect protein expression. RESULTS: UCA1 was highly expressed in GC tissues and cells, and knockdown of UCA1 increased chemosensitivity to cisplatin by inducing cell apoptosis. Furthermore, UCA1 promoted CYP1B1 expression by binding to miR-513a-3p in human GC cells in vitro, and UCA1/CYP1B1 expression was negatively related to miR-513a-3p expression, while UCA1 expression was positively related to CYP1B1 expression in human GC tissues. Moreover, overexpression of miR-513a-3p or knockdown of CYP1B1 increased chemosensitivity to cisplatin, and knockdown of miR-513a-3p or overexpression of CYP1B1 decreased chemosensitivity to cisplatin by inducing cell apoptosis in human GC cells. Importantly, overexpression of CYP1B1 reduced chemosensitivity to cisplatin which increased by knockdown of UCA1, and knockdown of CYP1B1 increased chemosensitivity to cisplatin which decreased by knockdown of miR-513a-3p in human GC cells. CONCLUSION: The lncRNA UCA1/miR-513a-3p/CYP1B1 axis regulates cisplatin resistance in human GC cells; hence, it is a potential target for treating chemoresistance in GC.

The association of elevated serum ferritin concentration in early pregnancy with gestational diabetes mellitus: a prospective observational study.

BACKGROUND/OBJECTIVES: The results linking body iron stores to the risk of gestational diabetes mellitus (GDM) are conflicting. We aimed to measure the serum ferritin level of women in early pregnancy and evaluate the risk of GDM in a Chinese urban population. SUBJECTS/METHODS: In total, 851 pregnant women between 10 and 20 weeks of gestation took part in the prospective, observational study conducted. The women were divided into four groups by quartiles of serum ferritin levels (Q1-4). Their blood samples were collected and assayed for several biochemical variables at the beginning of the study, and the women were followed up with a 75-g oral glucose tolerance test at 24-28 weeks of gestation. RESULTS: The participants had an average serum ferritin concentration of 65.67 µg/L. GDM prevalence within each serum ferritin quartile was 9.4%, 14.6%, 18.8% and 19.3%, respectively, (P = 0.016). The odds ratio for GDM in the ferritin Q2-4 was 1.64 (CI: 0.90-2.99), 2.23 (CI: 1.26-3.96) and 2.31 (CI: 1.30-4.10), compared with Q1, respectively. This association persisted after adjusting for potential confounders factors. In addition, in Q4, pregnant women with a pre-pregnancy body mass index ≥24 kg/m2, maternal age ≤35 years old or haemoglobin≥ 110 g/L did have an increased risk of developing GDM. CONCLUSIONS: Elevated serum ferritin concentrations in early gestation are associated with an increased risk of GDM, especially in pregnant women who have a high baseline iron storage status with no anaemia or who are overweight/obese. Individual iron supplementation should be considered to minimize the risk of GDM.

Portal vein thrombosis secondary to postoperative gastric cancer: Report of two cases.

Few cases of portal vein thrombosis secondary to gastric cancer surgery have been reported. Here we report the diagnosis and management of two such cases. Case 1: Gastric carcinoma with acute hematemesis was detected by endoscopy in the gastric body of a 48-year-old woman. Histologic examination revealed signet-ring cell carcinoma with marked invasion of the vessels and nerves. Laparoscopic partial gastrectomy and Roux-en-Y gastrogastrostomy were performed. One month after surgery, imaging examination showed the formation of thrombi in the main portal vein and the right hepatic vein. Case 2: Gastric carcinoma with pyloric obstruction was clinically diagnosed in a 66-year-old woman. Laparoscopic partial gastrectomy and Billroth Roux-en-Y gastrogastrostomy were again performed. Two months after surgery, an abdominal imaging examination detected a thrombus in the right hepatic vein. Clinicians should consider portal vein thrombosis in patients with hyperthermia combined with an abnormal increase in procalcitonin.

Long-Term Outcomes Comparison of Endoscopic Resection With Gastrectomy for Treatment of Early Gastric Cancer: A Systematic Review and Meta-Analysis.

Background: Endoscopic resection (ER) and gastrectomy have been both accepted as curative treatments for early gastric cancer. We intended to compare ER with gastrectomy treatments on safety of patients, disease-free survival and overall survival for early gastric cancer through this systematic review. Methods: A literature search was performed in Pubmed, Embase, and Cochrane Library databases. Studies that have compared ER with gastrectomy for early gastric cancer were included in this meta-analysis. We searched for clinical studies published before March 2019. Stata 12.0 software was used for systematic analysis. Results: Nine studies were included in this systematic review, ER treatment was associated with a shorter length of stay (WMD = -8.53, 95% CI -11.56 to -5.49), fewer postoperative complications (OR = 0.47, 95% CI 0.34-0.65). ER can be performed safely with shorter hospital stay and fewer postoperative complications than gastrectomy. Recurrence rate was higher for ER than for gastrectomy treatment (HR = 3.56, 95% CI 1.86-6.84), mainly because metachronous gastric cancers developed only in the ER treatment. However, most of the metachronous gastric cancers could be curatively treated with ER again, and it didn't affect overall survival of patients with early gastric cancer. There was no difference in overall survival rate between ER and gastrectomy (HR = 0.84, 95% CI 0.63-1.13). Conclusions: ER and gastrectomy are both acceptable for curative treatment of early gastric cancer. However, due to the comparable overall survival and lower postoperative complications and shorter length of stay, ER is better than gastrectomy for early gastric cancer, who met the indication for ER treatment.

Endothelin-A receptor in gastric cancer and enhanced antitumor activity of trastuzumab in combination with the endothelin-A receptor antagonist ZD4054.

Endothelin-A receptor (ETAR) is overexpressed in cancers and can function through transactivation of the epidermal growth factor receptor. We explored ETAR in gastric cancer and investigated the antitumor effect of trastuzumab in combination with the ETAR antagonist ZD4054. The expression of ETAR was significantly correlated with the expression of vascular endothelial growth factor. Univariate and multivariate analyses further showed that ETAR expression correlated with reduced survival in gastric cancer patients. In vitro, ZD4054 increased the antiproliferative effect of trastuzumab in gastric cancer cell lines. Moreover, the addition of ZD4054 to trastuzumab significantly increased apoptosis in gastric cancer cell lines. In vivo, tumor growth was considerably inhibited by treatment with ZD4054 and trastuzumab, and the tumor volume in the trastuzumab and ZD4054 combination group was smaller than in the other groups. The detection of ETAR could help predict the prognosis of gastric cancer patients. Additionally, this study provides support for the therapeutic use of the combination of ZD4054 and trastuzumab as an anticancer treatment, especially for gastric cancer.

Risk factors for recurrent macrosomia and child outcomes.

BACKGROUND: Women who had delivered a macrosomic newborn will have a higher risk to deliver another macrosomia. We aimed to examine the recurrence risk of macrosomia in the subsequent pregnancy and the implications in long-term child health. METHODS: Data from the Collaborative Perinatal Project, a longitudinal birth cohort with 54,371 singleton births, were used. 401 recurrent macrosomic infants (macro-macro) and 1327 normal weight babies with a macrosomia in the last pregnancy (macro-normal) were selected to explore risk factors for recurrent macrosomia. Furthermore, 768 newly onset macrosomia with normal birthweight infant in previous pregnancies (normal-macro) were identified to examine long-term health effects of recurrent macrosomia. RESULTS: The recurrent rate of macrosomia was 23.2% [95% confidence interval (CI) 21.2%, 25.2%]. White race, higher pre-pregnant body mass index (BMI), more gestational weight gain, male infant and more prior macrosomic infants were significant risk factors for recurrent macrosomia. At 4 years of age, recurrent macrosomic infants had a higher BMI (16.7 vs. 16.1 kg/m2, adjusted ß: 0.36, 95% CI: 0.12, 0.60) and a higher risk of overweight and obesity (adjusted OR: 1.56, 95% CI: 1.10, 2.23) than infants with normal birthweight after a previous macrosomic sibling. There was no significant difference between recurrent macrosomia and newly onset macrosomia in child outcomes after adjustment for covariates. CONCLUSIONS: Fetal macrosomia has a high recurrence rate in the following pregnancy. Higher maternal pre-pregnant BMI and gestational weight gain are still important risk factors for recurrence of macrosomia, which in turn increases the risk for childhood obesity.

Int6/eIF3e Silencing Promotes Placenta Angiogenesis in a Rat Model of Pre-eclampsia.

We investigated whether stable eukaryotic translation initiation factor 3e/inter 6 (eIF-3e/Int6) RNA-silencing (siRNA-Int6) can ameliorate pre-eclampsia (PE) by promoting angiogenesis in an N-nitro-L-arginine methyl ester (L-NAME)-induced rat pre-eclampsia (PE) model. Twenty-four pregnant female Sprague-Dawley rats were allocated into 4 groups, including controls (Con) without any treatment, and 18 from gestational day (GD) 7 to GD17 L-NAME-treated rats, which were divided into stable siRNA-Int6 transfected (siRNA-Int6), negative vector control siRNA (NC-siRNA) and PE control (PE-Con) groups. All adenovirus siRNA transfections were performed on GD7 via intravenous tail injection. On GD0, GD11 and GD17, blood pressure, and on GD6 and GD17, protein estimations in 24 h urine samples were conducted. All animals were sacrificed on GD18. In the PE-Con group, placental Int6 was expressed to a significantly greater level than in the Con group, which was reversed by the application of siRNA-Int6. Blood pressure and proteinuria were significantly lower in the siRNA-Int6 group than in the PRE-Con group. As shown by CD31 and IB4 expression, placental micro-vascular density (MVD) was significantly higher in the siRNA-Int6 group than in the PE-Con and NC-siRNA groups, which has accompanied by enhanced trophoblast invasion. Int6 silencing alleviated the maternal clinical manifestations of pre-eclampsia and promoted placental angiogenesis in pregnant L-NAME-treated rats.

The utility of HbA1c combined with haematocrit for early screening of gestational diabetes mellitus.

AIMS: To evaluate the utility of glycated haemoglobin A1c (HbA1c) alone and in combination with haematocrit (HCT) for screening gestational diabetes mellitus (GDM) between 12-16 gestational weeks. METHODS: This prospective study was carried out in the Obstetrics and Gynaecology Hospital of Fudan University from November 2014 to February 2015. In total, 690 pregnant women between 20 and 35 years old were included in this study. All subjects received a routine blood examination for HbA1c and HCT at 12-16 gestational weeks (gw) and a 75-g oral glucose tolerance test at 24-28 gw. Threshold values for the diagnosis of GDM were a plasma glucose concentration of 5.1 mmol/L after fasting, 10.0 mmol/L at 60 min, and 8.5 mmol/L at 120 min. Receiver operating characteristic curves were used to evaluate the diagnostic performance of HbA1c with or without HCT. RESULTS: One hundred seven women were diagnosis with GDM at 24-28 gw. An HbA1c cutoff value < 4.55% at 12-16 gw showed adequate sensitivity to exclude GDM (85.0%) but low specificity (17.3%), while an HbA1c cutoff value ≥ 5.25% presented adequate specificity (96.6%) but low sensitivity (13.3%) in diagnosing GDM. The area under the receiver operating characteristic curve for HbA1c (12-16 gw) detection of GDM was 0.563 (95% confidence interval [CI], 0.50-0.625). When combined HbA1c with HCT ( > 38.8%) for the screening of GDM, the area under the receiver operating characteristic curve was 0.604 (95% [CI] 0.509, 0.701). CONCLUSIONS: Whether the adoption of HbA1c as a screening test for GDM would benefit pregnant women remains to be determined. However, combining HbA1c with HCT for the screening of GDM may be a useful tool to predict GDM.