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Jinhui Cui,&ast; Ping Li,&ast; Xinjuan Chen, Ling Li, Liping Ouyang, Zhaoran Meng, Jianhui Fan Department of Obstetrics and Gynecology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianhui Fan, No. 600, Tianhe Road, Tianhe, Guangzhou, People’s Republic of China, Tel +86 18922102608, Email fanjh@mail.sysu.edu.cnObjective: To investigate the relationship and predictive value of first-trimester pregnancy-associated plasma protein A (PAPP-A), maternal factors, and biochemical parameters with gestational diabetes mellitus (GDM) in southern China mothers.Methods: This study recruited 4872 pregnant women. PAPP-A, the free beta subunit of human chorionic gonadotropin (free β-HCG), fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), and high- and low-density lipoproteins (HDL, LDL) were measured at 11– 13+ weeks of gestation. GDM was diagnosed based on a 75 g oral glucose tolerance test at 24– 28 weeks of gestation. We performed stepwise logistic regression analysis to determine the odds ratio (OR) and the 95% confidence interval (CI) of GDM. We used Receiver Operating Characteristic (ROC) curves with the area under the curve (AUC) to evaluate the predictive value of PAPP-A, maternal factors, and biochemical markers. The significance of the differences between the AUC values was assessed using the DeLong test.Results: GDM was diagnosed in 750 (15.39%) women. Independent factors for GDM were age, pre-gestational BMI, GWG before a diagnosis of GDM, previous history of GDM, family history of diabetes, FPG, TG, LDL, PAPP-A, and TC. The AUC of PAPP-A was 0.56 (95% CI 0.53– 0.58). The AUC of a model based on combined maternal factors, biochemical markers, and PAPP-A was 0.70 (95% CI 0.68– 0.72). Differences in AUC values between PAPP-A alone and the model based on combined maternal factors, biochemical markers, and PAPP-A were statistically significant (Z= 9.983, P< 0.001).Conclusion: A Low serum PAPP-A level in the first trimester is an independent risk factor for developing GDM later in pregnancy. However, it is not a good independent predictor although the predictive value of a low serum PAPP-A level increases when combined with maternal factors and biochemical markers.Keywords: gestational diabetes mellitus, pregnancy-associated plasma protein-A, maternal factors, biochemical markers, predictive value

Background: Maternal subclinical hypothyroidism (SCH) has been associated with adverse pregnancy outcomes. This study aimed to explore whether SCH in the first trimester contributed to the developm...

The successful implantation of embryos is crucial for pregnancy in mammals. This complex process is inevitably dependent on the development of the endometrium. The Paired-like homeodomain transcription factor 2 (PITX2) is involved in a variety of biological processes, but whether it is involved in embryo implantation has not been reported. In this study, we aimed to investigate uterine expression and regulation of PITX2 during implantation. We found that PITX2 was elevated in the human endometrium in the secretory phase. The results of the pregnant mouse models showed that PITX2 expression was spatiotemporal in mouse endometrial tissue throughout peri-implantation period, and it was significantly upregulated at the time of implantation. Interestingly, PITX2 was mainly localized to the glandular epithelium cells on D2.5-3.5 of pregnancy, while D5.5-6.5 was largely expressed in stromal cells. In vitro, PITX2 regulated endometrial cells proliferation, migration, invasion and other functions through the Wnt/β-catenin signaling pathway. In addition, a significant decrease in the rate of embryo implantation was observed after injecting PITX2 siRNA into the uterine horn. These results demonstrate the effects of PITX2 on the physiological function of endometrial cells and embryo implantation, suggesting a role in the endometrial regulatory mechanism during implantation. This article is protected by copyright. All rights reserved.

Phospholipase A2 enzymes (PLA2s) comprise a superfamily that is generally divided into six subfamilies known as cytosolic PLA2s (cPLA2s), calcium-independent PLA2s (iPLA2s), secreted PLA2s (sPLA2s), lysosomal PLA2s, platelet-activating factor (PAF) acetylhydrolases, and adipose specific PLA2s. Each subfamily consists of several isozymes that possess PLA2 activity. The first three PLA2 subfamilies play important roles in inflammation-related diseases and cancer. In this review, the roles of well-studied enzymes sPLA2-IIA, cPLA2α and iPLA2β in carcinogenesis and cancer development were discussed. sPLA2-IIA seems to play conflicting roles and can act as a tumor suppressor or a tumor promoter according to the cancer type, but cPLA2α and iPLA2β play protumorigenic role in most cancers. The mechanisms of PLA2-mediated signal transduction and crosstalk between cancer cells and endothelial cells in the tumor microenvironment are described. Moreover, the mechanisms by which PLA2s mediate lipid reprogramming and glycerophospholipid remodeling in cancer cells are illustrated. PLA2s as the upstream regulators of the arachidonic acid cascade are generally high expressed and activated in various cancers. Therefore, they can be considered as potential pharmacological targets and biomarkers in cancer. The detailed information summarized in this review may aid in understanding the roles of PLA2s in cancer, and provide new clues for the development of novel agents and strategies for tumor prevention and treatment.

Hypersonic laminar flow over a canonical 25°–55° double cone is studied using computational fluid dynamics and global stability analysis (GSA) with a free-stream Mach number of 11.5 and various unit Reynolds numbers. Axisymmetric simulations reveal that secondary separation occurs beneath the primary separation bubble beyond a critical Reynolds number. The numerical results agree well with existing experiments and the triple-deck theory with the axisymmetric effect on the incoming boundary layer treated by the Mangler transformation. The GSA identifies a three-dimensional global instability that is azimuthally periodic immediately prior to the emergence of secondary separation. The criterion of the onset of global instability in terms of a scaled deflection angle established for supersonic compression corner flows (Hao et al., J. Fluid Mech., vol. 919, 2021, A4) can be directly applied to double-cone flows. As the Reynolds number is further increased, the flow is strongly destabilized with the coexistence of multiple stationary and low-frequency oscillating unstable modes. Direct numerical simulations confirm that the supercritical double-cone flow is intrinsically three-dimensional, unsteady and exhibits strong azimuthal variations in the peak heating.

Hepatocellular carcinoma (HCC) is a particularly heterogeneous tumor. It has a very poor prognosis. Pyroptosis has been demonstrated in recent years to be an inflammatory form of programmed cell death. However, the relationship between the expression of pyroptosis related genes (PRGs) and prognosis of HCC is still unclear. The development of a specific PRGs prognostic model is important if we want to improve therapeutic effect of tumor. In this study, we identified 42 PRGs that were differentially expressed between HCC and peripheral normal tissues and exhibited the mutation frequency, classification, the location of copy number variation (CNV) alteration and the CNV variation frequency of PRGs. Two clusters were distinguished by the consensus clustering analysis based on the 42 differentially expressed genes (DEGs). The result show that there were significant differences in clinical features (including T stage, grade, gender, stage) among different clusters. KM curve analysis show that cluster 1 had a better prognosis than cluster 2. The prognostic value of PRGs for survival was evaluated to construct a multigene signature using The Cancer Genome Atlas (TCGA) cohort. By applying the univariate analysis and multivariate analysis method, a 10-gene signature was built and all HCC patients in the TCGA cohort were divided into low-risk group and high-risk group. HCC patients in the high-risk group showed significantly lower survival possibilities than those in the low-risk group (P

Hypersonic laminar flow over a canonical 25–55° double cone is studied using computational fluid dynamics, bispectrum analysis, and dynamic mode decomposition (DMD) with a freestream Mach number of 11.5 and unit Reynolds number of [Formula: see text]. The present study focuses on the evolution and nonlinear behavior of perturbation modes in the flow. The presence of the perturbation modes is first described in detail through the results of direct numerical simulation. The results of high-order spectrum analysis (bispectrum) then reveal complex nonlinear interactions in the flow. By examining the evolution of such interactions, the frequency broadening phenomenon of the fully saturated flow is explained, and the unsteady dynamics of the fully saturated flow are recognized to be caused by the nonlinear saturation of linear instability in the flow. This causality is further confirmed by the DMD results of the Stanton number near the reattachment region. The origins and dynamics of unsteady saturated flow in the hypersonic laminar flow are, therefore, demonstrated.

BackgroundHydatidiform mole is a disease caused by abnormal proliferation of trophoblastic cells. MiR-30a acts as a tumor suppressor gene in most tumors and participates in the development of various cancers. But its role in hydatidiform mole is not clear. MethodsRT-qPCR was used to verify the expression level of miR-190 and STOX2. Flow cytometry (FCM) assays were performed to detect cell cycle. CCK-8 assay, EDU assay and colony formation assay was used to detect proliferation ability. Transwell assay was used to test invasion ability. Dual-luciferase reporter assay and Western blotting were used to elucidate the potential mechanisms involved.ResultThe low expression of miR-30a promoted the ability of proliferation, migration and invasion in trophoblastic cells (JAR and HTR-8). The dual luciferase assay confirmed that STOX2 was a new target of miR-30a and resisted the effect of up-regulated miR-30a in trophoblastic cells. In addition, up-regulation of STOX2 by miR-30a could activate ERK, AKT and P38 signaling pathways. These results revealed that a new mechanism for ERK, AKT and P38 activation by miR-30a/STOX2, which could create excessive proliferation of trophoblast cells in the hydatidiform mole.Conclusions In this study, we found that miR-30a plays an important role in the development of HM. Taken together, these fndings indicate that miR-30a may effect the malignant transformation of human trophoblastic cells by downregulating STOX2, which strengthens our understanding of miR-30a in regulating BC cell transformation.

Organic cation transporter member 2 (OCT2) is an N-glycosylated transporter that has been shown to be closely associated with the transport of antitumor drugs. Oxaliplatin, a platinum-based drug, is used for the chemotherapy of colorectal cancer (CRC). However, oxaliplatin resistance is a major challenge in the treatment of advanced CRC. The aim of the present study was to better understand the mechanism underlying the chemosensitivity of CRC cells to oxaliplatin. The present study describes a potential novel strategy for enhancing oxaliplatin sensitivity involving the glycosylation of this drug transporter, specifically the modification of β-1,6-N-acetylglucosamine (GlcNAc) residues by N-acetylglucosaminyltransferase V (GnT-V). The results revealed that the downregulation of GnT-V inhibited the oxaliplatin chemosensitivity of CW-2 cells. Furthermore, the knockdown of GnT-V caused a marked reduction in the presence of β-1,6-GlcNAc structures on OCT2 and decreased the localization of OCT2 in the cytomembrane, which were associated with a reduced uptake of oxaliplatin in wild-type and oxaliplatin-resistant CW-2 cells. Overall, the study provides novel insights into the molecular mechanism by which GnT-V regulates the chemosensitivity to oxaliplatin, which involves the modulation of the drug transporter OCT2 by N-glycosylation in CRC cells.

This study aims to evaluate the relationship between subclinical hypothyroidism (SCH) during the first trimester and gestational diabetes mellitus (GDM) that was happened later on in our cohort. A total of 6530 pregnant women who first visited before 13+6 gestational weeks and accepted routinely prenatal services in the third affiliated hospital of Sun Yat-Sen University from January 2015 to September 2018 were finally met the inclusion criteria and recruited. Thyroid functions were performed at the first visit and a 2h 75-g OGTTwas performed between 24-28 weeks. The glucose levels of OGTT were shown no differences between SCH and euthyroid women [0 hour: 4.17 mmol/L (3.99-4.38) vs. 4.16 mmol/L (3.97-4.39), P = 0.730; 1 hour: 7.61 mmol/L (6.64-8.66) vs. 7.68 mmol/L (664-8.75), P = 0.449; 2 hour: 6.66 mmol/L (5.85-7.68) vs. 6.75 mmol/L (5.93-7.74), P = 0.142]. The incidence of GDM was no change as the TSH level increased in either TPOAb negative or positive SCH women (all P > 0.05). After using the multivariate logistic regression analysis adjusted for confounders (maternal age, educational levels and preBMI), elevated TSH and TPOAb status also had no effect on the incidence of GDM (Table 1). These results suggested maternal SCH in the first trimester was not related to GDM, regardless of the TPOAb status or the TSH levels. Disclosure P. Li: None. S. Lin: None. J. Fan: None. Funding Science and Technology Planning Project of Guangdong Province (2017A020215026); Medical Scientific Research Foundation of Guangdong Province (A2017314)

This study aims to evaluate the association of muscle/fat mass ratio in the first trimester with gestational diabetes mellitus (GDM) in Chinese subjects. A total of 3011 pregnant women were recruited from our hospital, Guangzhou, China, from Jan 2017 to Dec 2017. The muscle/fat mass ratio (< 13+6 weeks’ gestation) and 75-g OGTT (24-28 weeks’ gestation) were measured in each subject. The muscle/fat mass ratio was assessed by bioelectrical impedance analysis. GDM was diagnosed according the IADPSG guideline (2010). All subjects had average age 29 years (interquartile range:27-32 years), mean pregestational body mass index 20.7±2.6kg/m2, muscle/fat mass ratio 2.64±0.65. Five hundred and forty eight subjects (17.9%) were diagnosed as GDM. The prevalence of GDM were 25.9%, 20.4%, 14.1%, and 11.3% among subjects with muscle/fat mass ratio in 1st quartile (≤2.15), 2nd quartile (2.16-2.61), 3rd quartile (2.62-3.08), and 4th quartile(≥3.09), respectively. The prevalence of GDM decreased while muscle/fat mass ratio increased. The area under ROC curve was 0.612 (0.595-0.630) for the muscle/fat mass ratio in predicting GDM (P Disclosure P. Li: None. S. Lin: None. J. Fan: None. L. Zeng: None. Funding Science and Technology Planning Project of Guangdong Province (2017A020215026); Medical Scientific Research Foundation of Guangdong Province (A2017314)

Background: To explore the association between subclinical hypothyroidism (SCH) during the first trimester and gestational diabetes mellitus (GDM) that was happened later on in our cohort. Methods: A total of 6530 pregnant women who first visited before 13 +6 gestational weeks and accepted routinely prenatal services in the third affiliated hospital of Sun Yat-Sen University from January 2015 to September 2018 were finally met the inclusion criteria and recruited. Thyroid functions (TSH, free T4 (FT4) and TPOAb) were performed at the first visit and a 2h 75-g oral glucose tolerance test was performed between 24-28 weeks. Chi-square test and multivariate logistic regression were used to evaluate the association between SCH and GDM. Results: Though SCH group was divided into subgroups according TPOAb status and TSH levels, the incidence of GDM was no change when compared with the normal group (all P > 0.05). No matter adjusting or not for maternal age, maternal pregestational body max index, parity and educational level, the results showed elevated TSH was not associated GDM (all P > 0.05). TPOAb status also had no effect on the incidence of GDM either before or after adjustment ( P > 0.05). Conclusion: Maternal SCH in the first trimester was not associated with GDM, regardless of the TPOAb status or the TSH levels.

Lactobacillus reuteri FN041 is a secretory IgA–targeted Lactobacillus strain from human breast milk that has probiotic potential. The aim of this study was to test whether FN041 can alleviate dyslipidaemia and mucosal-barrier damage caused by a high-fat diet (HFD) and whether it can affect diurnal variation of the intestinal microbiota. C57BL/6 mice were fed either a normal chow diet or high-fat diet (HFD) for 7 weeks and were treated with either PBS as a control or L. reuteri FN041 for 4 weeks. Our results showed that FN041 treatment significantly attenuated HFD-induced weight gain (P < 0.01), accumulation of testicular fat, an increase in locomotor activity during the active phase (P < 0.01), triglyceridaemia, hypercholesterolaemia (P < 0.05), liver Fas overexpression, and Srebp1c mRNA expression inhibition. Moreover, FN041 treatment improved intestinal epithelial barrier function and induced a daily oscillation–dependent change in short-chain fatty acid production by the gut microbiota. A deeper understanding of the molecular pathways participating in intestinal barrier and microbiota modifications, and changes to lipid metabolism under the influence of FN041, will have important implications by potentially opening new horizons for the development of relevant foods to prevent metabolic disorders and unrelated intestinal diseases.

Objective: To evaluate the usefulness of a fasting plasma glucose (FPG) at the first trimester in predicting gestational diabetes mellitus (GDM) and the association between FPG and adverse pregnancy outcomes. Methods: The levels of FPG in women with singleton pregnancies were measured at 9-13+6 weeks. A two hour 75-g oral glucose tolerance test (OGTT) was completed at 24-28 weeks and the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria was used. Adverse pregnancy outcomes were assessed and recorded. Results: Among 2112 pregnant women enrolled in the study, 224 (10.6%) subjects were diagnosed with GDM. The AUC for FPG in predicting GDM was 0.63 (95% CI 0.61- 0.65) and the optimal cutoff value was 4.5 mmol/L (sensitivity 64.29% and specificity 56.45%). Higher first-trimester FPG increased the prevalence of GDM, large for gestational age (LGA) and assisted vaginal delivery and/or cesarean section (all P < 0.05). Conclusion: FPG at first trimester could be used to predict GDM and higher first-trimester FPG was associated with adverse pregnancy outcomes.

Hepatocellular carcinoma (HCC) treatment remains lack of effective chemotherapeutic drugs, therefore, discovering novel anti-HCC drugs is a very attractive and urgent task. In this study, we reported VOSL (volatile oil from Saussurea lappa root) exhibits potent therapeutic effect on SMMC-7721 xenografts without obvious side effects. In the in vitro experiments, VOSL inhibited HCC cell proliferation by arresting cell cycle at S and G2/M phases, and induced HCC cell apoptosis by activating the Caspase3 pathway. VOSL also decreased the capability of HCC cell migration and invasion through MMP-9 depression. Moreover, mechanistic study indicated that VOSL can act as an epithelial growth factor receptor (EGFR) inhibitor to suppress EGFR activation and then to suppress its downstream MEK/P38 and PI3-K/Akt pathways. These results suggested that VOSL may be a novel anti-HCC drug candidate.

Objective To evaluate the value of Model for end-stage liver disease (MELD) in assessing the prognosis of acute fatty liver of pregnancy (AFLP). Study design This was a retrospective study. From January 2010 to July 2018, data of 53 women diagnosed with AFLP in the third affiliated hospital of Sun Yat-Sen University were collected. Blood samples were collected on admission and MELD score was calculated. The MELD score was calculated by using the original MELD formula as shown: 9.57 log (creatinine) + 3.78 log (bilirubin) + 11.20 log (international normalized ratio, INR) + 6.43. The perinatal outcomes were documented. Results Nine women were excluded as they were transfered to our hospital after delivery in other hospitals. The remaining 44 women had average age of 28.8 ± 5.2 years. The MELD score showed good performance in predicting most of the perinatal complications of AFLP with all the area under the receiver operating characteristic (ROC) curves (AUC) > 0.8, including ascites (AUC: 0.91, 95% CI: 0.78–0.98), wound seroma (AUC: 0.91, 95% CI: 0.78–0.93), hepatic encephalopathy (AUC: 0.93, 95% CI: 0.82–0.99), DIC (AUC: 0.87, 95% CI: 0.74–0.95), sepsis (AUC: 0.93, 95% CI: 0.82–0.99), renal insufficiency (AUC: 0.94, 95% CI: 0.82–0.99) and stillbirth (AUC: 0.85, 95% CI: 0.71–0.94). Nearly all the maternal complications were more frequently happened in MELD score ≥30 group (P Conclusion MELD scoring system may be a suitable method for assessing the prognosis of AFLP.

Objective: To evaluate the usefulness of a fasting plasma glucose (FPG) at the first trimester in predicting gestational diabetes mellitus (GDM) and the association between FPG and adverse pregnancy outcomes. Methods: The levels of FPG in women with singleton pregnancies were measured at 9-13+6 weeks. A two hour 75-g oral glucose tolerance test (OGTT) was completed at 24-28 weeks and the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria was used. Adverse pregnancy outcomes were assessed and recorded. Results: Among 2112 pregnant women enrolled in the study, 224 (10.6%) subjects were diagnosed with GDM. The AUC for FPG in predicting GDM was 0.63 (95% CI 0.61- 0.65) and the optimal cutoff value was 4.5 mmol/L (sensitivity 64.29% and specificity 56.45%). Higher first-trimester FPG increased the prevalence of GDM, large for gestational age (LGA) and assisted vaginal delivery and/or cesarean section (all P < 0.05). Conclusion: FPG at first trimester could be used to predict GDM and higher first-trimester FPG was associated with adverse pregnancy outcomes. How to cite this:Li P, Lin S, Li L, Cui J, Zhou S, Fan J. First-trimester fasting plasma glucose as a predictor of gestational diabetes mellitus and the association with adverse pregnancy outcomes. Pak J Med Sci. 2019;35(1):95-100. doi: https://doi.org/10.12669/pjms.35.1.216 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background To investigate the effect of a mildly elevated thyroid-stimulating hormone (TSH) concentration between 2.5 and 4.0 mIU/L during the first trimester on pregnancy outcomes in thyroid peroxydase antibody (TPOAb)-negative pregnant women. Methods A total of 1858 pregnant women who were TPOAb-negative before 13+ 6 gestational weeks, received regular prenatal services, and delivered in the third affiliated hospital of Sun Yat-Sen University were recruited from June 2016 to June 2017. Measurements of thyroid function (TSH, free T4 [FT4] and TPOAb) and adverse pregnancy outcomes were assessed and recorded. Results Among the 1858 study participants, the 97.5th percentile for TSH was 3.76 mIU/L, and 142 women (7.6%) had mildly elevated TSH levels between 2.5 and 4.0 mIU/L. No differences in the incidence of adverse pregnancy outcomes were observed between patients with a mildly elevated TSH level and those with a normal TSH level (

Human equilibrative nucleoside transporter 1 (hENT1) transports nucleoside analogue drugs across cellular membranes and is necessary for the uptake of many anti-tumor drugs. Gemcitabine is a frontline agent of chemotherapy for bladder cancer despite its limited efficacy due to chemoresistance, there is an acute need to decipher mechanisms underlying chemosensitivity to gemcitabinein in bladder cancer cells. Here we report a novel role for N-acetylglucosaminyltransferase V (GnT-V) in gemcitabine chemosensitivity. In this study, we found that GnT-V expression affected cell death rate to gemcitabine in different bladder cancer cells and down-regulation of GnT-V inhibited the gemcitabine sensitivity with time and dose dependent way in T24 cells. Moreover, mechanistic investigations showed that silencing GnT-V caused dramatic decrease of β1,6 GlcNAc structure on hENT1 leading to apparently decreased accumulation of hENT1 at plasma membrane, and therefore result in less uptake of gemcitabine in T24/shRNA cells. Together, our present study indicated that GnT-V enhances gemcitabine chemosensitivity via modulation of hENT1 N-glycosylation and transport activity in T24 cells, providing new insights into how N-glycosylation drives antitumor drug sensitivity during chemotherapy for patients with cancer.

This study aims to evaluate the usefulness of a fasting plasma glucose (FPG) at the first trimester in predicting gestational diabetes mellitus (GDM) and the association between FPG and adverse pregnancy outcomes in Chinese women. Medical records of 2112 singleton pregnant women were collected from the third affiliated hospital of Sun Yat-Sen University, Guangzhou, China, from January 2016 to June 2017. FPG was measured at 9-13+6 weeks and 75 g oral glucose tolerance test (OGTT) was performed at 24-28 weeks in each subject. The International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria was used for diagnosing GDM. Among 2112 subjects, 224 (10.6%) subjects were diagnosed with GDM. The area under ROC curve (AUC) for FPG in predicting GDM was 0.63 (95% CI 0.61- 0.65) and the optimal cutoff value 4.5 mmol/L (sensitivity 64.29% and specificity 56.45%) (Figure 1). Higher first-trimester FPG increased the incidences of GDM, large for gestational age (LGA) and assisted vaginal delivery and/or cesarean section (all P > 0.05). These results suggested FPG at first trimester could be used to predict GDM and higher first-trimester FPG was associated with adverse pregnancy outcomes. Disclosure P. Li: None. S. Lin: None. L. Li: None. J. Cui: None. J. Fan: None.

Our study aims to evaluate the correlations between thyroid hormone levels in early pregnancy and the incidence of gestational diabetes mellitus (GDM). A total of 2112 pregnant women were recruited from our hospital, Guangzhou, China, from June 2016 to June 2017. Fasting plasma glucose (FPG), Thyrotropin (TSH), free T4 (FT4), and thyroid peroxydase antibody (TPO-Ab) were measured at 9-14 weeks’ gestation (first trimester) and 75-g OGTT (24-28 weeks’ gestation) were performed in each subject. Diagnosis of GDM was made by the IADPSG guideline (2010). All subjects had median age of 30 years (interquartile range:27-34 years). Two hundred and twenty four subjects (10.6%) were diagnosed as GDM. GDM women had older age and higher FPG(P0.05). The prevalence of GDM in subjects among different quartiles of FT4 levels were 11.9%, 11.5%, 9.5% and 9.5% from the first to fourth quartile (P=0.429,χ2=2.766). By using logistic regression, FT4 in the first trimester odds ratios for GDM were not significant: OR 0.970 [95% CI 0.931-1.011] (unadjusted) and 0.960[95% CI 0.920-1.002] (adjusted for age, TSH, TPO-Ab). Our results indicated the level of FT4 in the first trimester may not have strong correlation with incidence of GDM. Disclosure P. Li: None. S. Lin: None. L. Li: None. L. Ouyang: None. J. Fan: None.

Ribonuclease inhibitor (RI), also termed angiogenin inhibitor, acts as the inhibitor of ribonucleolytic activity of RNase A and angiogenin. The expression of RI has been investigated in melanoma and bladder cancer cells. However, the precise role of RI in tumorigenesis, in addition to RI‑induced autophagy, remains poorly understood. In the present study, it was demonstrated that RI positively regulated autophagy in human colorectal cancer (CRC) cells as indicated by an increase in light chain 3 (LC3)‑II levels. Furthermore, RI regulated cell survival in HT29 cells. In addition, autophagy‑associated proteins, including beclin‑1 and autophagy‑related protein 13, were increased in response to RI‑induced autophagy, and the protein kinase B (Akt)/mechanistic target of rapamycin (mTOR)/Unc‑51 like autophagy activating kinase (ULK1) pathway may be involved in the activation of autophagy induced by RI overexpression. Taken together, the evidence of the present study indicated that the overexpression of RI induced ATG‑dependent autophagy in CRC cells via the Akt/mTOR/ULK1 pathway, suggesting that the upregulation of RI activity may constitute a novel approach for the treatment of human colorectal carcinoma.

A karst analog model has been developed for simulating karst aquifer systems with fracture and conduit domains in the laboratory. In this study, sixty-four experiments under different recharging and discharging conditions were carried out with the analog setup to study flow in the karst analog model. The experiments did not only provide hydraulic head data but spring discharge process as well. The experimental results were used to obtain empirical models of water hydraulic head under different hydrological conditions, which together with the spring discharge analysis aided in developing a water hydraulic head prediction model for the analog model. The results showed that water hydraulic head increased with logarithm of time and declined in step-shaped style, which can be used in karst aquifer systems research. Consequently, the study provides useful information for a better understanding of flow in karst aquifer systems.

Much evidence suggested that quantitative analysis of bile acids (BAs), lysophosphatidylcholines (LPCs), and polyunsaturated fatty acids (PUFAs) in biofluids may be very useful for diagnosis and prevention of hepatobiliary disease with a non-invasive manner. However, simultaneously fast analysis of these metabolites has been challenging for their huge differences of physicochemical properties and concentration levels in biofluids. In this study, we present a liquid chromatography–mass spectrometry method with a high throughput analytical cycle (10 min) to fast and accurately quantify fifteen potential biomarkers (eight BAs, four LPCs and three PUFAs) of hepatobiliary disease. The accuracy for the fifteen analytes in plasma and urine matrices was 80.45%–118.99% and 84.55%–112.66%, respectively. The intra- and inter- precisions for the fifteen analytes in plasma and urine matrices were all less than 20% and the lower limit of quantification (LLOQ) of analytes is up to 0.0283–8.2172 nmol/L. Therefore, this method is fast, sensitive and accurate for the quantitative analysis of BAs, LPCs and PUFAs in biofluids. Moreover, the stability and concentration differences of the analytes in plasma and serum were evaluated, and the results demonstrated that LPCs is stable, but PUFAs is very unstable in freeze and thaw cycles, and the concentrations of the analytes in serum were slightly higher than those in plasma. We suggested plasma may be a kind of better bio-sample than serum using for quantitative analysis of metabolites in blood, due to the characteristics of plasma are more close to blood than those of serum.

Backgrounds This study aimed to evaluate the relationship between neck circumference (NC) and gestational diabetes mellitus (GDM), and the efficacy of NC in predicting GDM by comparing with pregestational body mass index (preBMI) in southern Chinese woman. Marerials and Methods A total of 371 pregnant women (97 GDM and 274 normal pregnant women) were recruited from the third affiliated hospital of Sun Yat-Sen University, Guangzhou, China. NC was measured at 11-13+6 gestational weeks. GDM was diagnosed through a 75-g oral glucose tolerance test at 24-28 gestational weeks. Using the receiver-operator characteristic (ROC) curve analysis, we evaluated the association between NC and GDM. Results The area under the receiver operator characteristic curves were 0.65 (95% CI: 0.60-0.70) for NC and 0.64 (95% CI: 0.59-0.69) for preBMI in diagnosing GDM and no difference was found between them (P = 0.66). NC ≥ 33.8 cm was determined to be the best cut-off level for identifying subjects with GDM (sensitivity 68.04% and specificity 59.12%). Multivariate logistic regression analysis showed that a large NC in the first trimester was an independent risk factor for the development of GDM (odds ratio [OR] = 1.29, 95% CI: 1.72-7.45). Conclusions NC, as well as preBMI, might be a novel anthropometric index for GDM screening. The increase of NC could be an independent risk factor for GDM in first trimester pregnancy.

Aberrant glycosylation may promote tumor invasion and metastasis. To investigate whether microRNA (miRNA) is involved in glycosylation-related metastasis, we examined the role of let-7c, a well-known tumor-suppressor miRNA, in glycosylation in murine hepatocarcinoma cell lines Hca-F and Hca-P. We found that let-7c level was higher in Hca-P cells (with lower lymphatic metastasis potential) than in Hca-F cells (with higher lymphatic metastasis potential). Overexpression of let-7c decreased hyper-N-glycosylation of Hca-F cells and repressed their metastatic and invasive ability. Mannoside acetylglucosaminyltransferase 4, isoenzyme A (Mgat4a) is a key glycosyltransferase in the pathway of synthesizing complex N-glycans. Bioinformatics analysis indicates that Mgat4a may be a target of let-7c, which has been verified by dual-luciferase reporter gene assay. Furthermore, the anti-metastatic effect of overexpressed let-7c is similar to that of Mgat4a siRNAs transfection. Hence, our results suggest that let-7c may inhibit the metastatic ability of Hca-F cells, at least partially, via repressing Mgat4a activity.