Maternal circulating metabolic biomarkers and their prediction performance for gestational diabetes mellitus related macrosomia.

INTRODUCTION: Gestational diabetes mellitus (GDM), a metabolism-related pregnancy complication, is significantly associated with an increased risk of macrosomia. We hypothesized that maternal circulating metabolic biomarkers differed between women with GDM and macrosomia (GDM-M) and women with GDM and normal neonatal weight (GDM-N), and had good prediction performance for GDM-M. METHODS: Plasma samples from 44 GDM-M and 44 GDM-N were analyzed using Olink Proseek multiplex metabolism assay targeting 92 biomarkers. Combined different clinical characteristics and Olink markers, LASSO regression was used to optimize variable selection, and Logistic regression was applied to build a predictive model. Nomogram was developed based on the selected variables visually. Receiver operating characteristic (ROC) curve, calibration plot, and clinical impact curve were used to validate the model. RESULTS: We found 4 metabolism-related biomarkers differing between groups [CLUL1 (Clusterin-like protein 1), VCAN (Versican core protein), FCRL1 (Fc receptor-like protein 1), RNASE3 (Eosinophil cationic protein), FDR <  0.05]. Based on the different clinical characteristics and Olink markers, a total of nine predictors, namely pre-pregnancy body mass index (BMI), weight gain at 24 gestational weeks (gw), parity, oral glucose tolerance test (OGTT) 2 h glucose at 24 gw, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) at 24 gw, and plasma expression of CLUL1, VCAN and RNASE3 at 24 gw, were identified by LASSO regression. The model constructed using these 9 predictors displayed good prediction performance for GDM-M, with an area under the ROC of 0.970 (sensitivity = 0.955, specificity = 0.886), and was well calibrated (P Hosmer-Lemeshow test = 0.897). CONCLUSION: The Model included pre-pregnancy BMI, weight gain at 24 gw, parity, OGTT 2 h glucose at 24 gw, HDL and LDL at 24 gw, and plasma expression of CLUL1, VCAN and RNASE3 at 24 gw had good prediction performance for predicting macrosomia in women with GDM.

Association of Maternal Serum 25-Hydroxyvitamin D Concentrations with Risk of Gestational Anemia.

BACKGROUND/AIMS: Vitamin D deficiency has been shown to be associated with a greater prevalence of anemia in various healthy and diseased populations by a great deal of observational studies. However, less work has been done to explore this association in pregnant women. The aim of this study was to evaluate the association between maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations and risk of gestational anemia in a large, nested case-control study. METHODS: The serum 25(OH)D concentrations was measured by enzyme immunoassay in 775 pregnant women affected with anemia and 1550 controls. Logistic regression analysis was conducted to assess the association of 25(OH)D concentrations with risk of gestational anemia. RESULTS: We found the 25(OH)D concentrations was significantly lower in women affected with anemia than in controls. Logistic regression analyses showed that women with 25(OH)D concentrations < 25.0 nmol/L, from 25.0 to 37.4 nmol/L and from 37.5 to 49.9 nmol/L all had increased risk of anemia when compared with women with concentrations from 50.0 to 74.9 nmol/L. And the risk of anemia was significantly increased with the decreasing concentrations of the serum 25(OH)D in a dose-dependent manner (P for trend = 0.012). For women with concentrations < 50.0 nmol/L, they had an 80% increase in anemia risk (95% CI = 1.45-2.25) after adjustment for confounders. We also observed a nonlinear relationship between the serum 25(OH)D and anemia, with a threshold for 25(OH)D of 50.0 nmol/L existed for anemia. CONCLUSION: Maternal serum 25(OH)D < 50.0 nmol/L may be a risk factor for gestational anemia, and it should be monitored for the high-risk pregnant women.

Association of Maternal Serum 25-hydroxyvitamin D Concentrations in Second Trimester with Delivery Mode in A Chinese Population.

Objective: To determine the maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations in a Chinese population and investigate its associations with subsequent delivery mode by studying 1924 unrelated pregnant women. Methods: The serum 25(OH)D concentrations was measured by euzymelinked immunosorbent assay (ELISA). Simultaneously, maternal information and subsequent delivery mode were collected. Logistic regression analysis was performed to assess the associations between 25(OH)D concentrations and caesarean section. Results: The median (IQR) serum concentration of 25(OH)D for the total subjects was 43.4 (35.2-56.9) nmol/L. Among them, 1225 (63.7%) women were in the status of 25(OH)D deficiency (< 50.0 nmol/L). The 25(OH)D concentrations showed significant variation by body mass index (BMI), parity and season of sampling. Women with caesarean section was older, and with higher BMI and rate of abnormal pregnancy history, suggesting advanced age, obesity and abnormal pregnancy history may be the risk factors for the subsequent caesarean section. Compared with 25(OH)D from 50.0 to 74.9 nmol/L, women with low 25(OH)D concentrations (< 50.0 nmol/L) was not significantly associated with caesarean section. Only in the subgroup of the women without abnormal pregnancy history, higher 25(OH)D (> 75.0 nmol/L) concentrations could significantly decrease the risk of caesarean section. Conclusion: Vitamin D deficiency is a quite serious problem in Chinese pregnant women. There is no evidence that the maternal serum 25(OH)D concentrations is associated with increased risk of caesarean section.

[Values of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in predicting sensitivity to intravenous immunoglobulin in Kawasaki disease].

OBJECTIVE: To study the values of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in predicting the sensitivity to intravenous immunoglobulin (IVIG) in Kawasaki disease (KD). METHODS: A retrospective cohort study was conducted in 404 children with newly diagnosed KD. The data on routine blood tests, NLR, and PLR were collected before and after IVIG treatment. The receiver operating characteristic (ROC) curve was used to determine the cut-off values of NLR and PLR in predicting the insensitivity to IVIG. A logistic regression analysis was used to identify independent predictive factors for insensitivity to IVIG. RESULTS: Of all patients, 31 were insensitive to IVIG. Compared with the IVIG sensitivity group, the IVIG insensitivity group had a significantly higher incidence rate of coronary artery ectasia (P<0.01), a shorter course of disease when IVIG therapy was initiated (P<0.05), and significantly higher NLR, PLR, and C-reactive protein (CRP) level before and after treatment (P<0.05). The optimal cut-off values for NLR and PLR to predict IVIG insensitivity were 4.36 and 162 before IVIG treatment and 1.45 and 196 after treatment. The multivariate regression analysis showed that the course of disease before IVIG treatment, CRP before IVIG treatment, and NLR and PLR before and after IVIG treatment were independent predictive factors for IVIG insensitivity. CONCLUSIONS: NLR and PLR can be used to predict IVIG insensitivity in children with KD.

The diagnostic performance in clinically significant prostate cancer with PI-RADS version 2.1: simplified bpMRI versus standard mpMRI.

OBJECTIVES: To compare the diagnostic performance for the detection of clinically significant prostate cancer (csPCa) between bpMRI with only axial T2WI (simplified bpMRI) and standard-multiparametric MRI (mpMRI). METHODS: A total of 569 patients who underwent mpMRI followed by biopsy or prostatectomy were enrolled in this retrospective study. According to PI-RADS v2.1, three radiologists (A, B, C) from three centers blinded to clinical variables were assigned scores on lesions with simplified bpMRI and then with mpMRI 2 weeks later. Diagnostic performance of simplified bpMRI was compared with mpMRI using histopathology as reference standard. RESULTS: For all the three radiologists, the diagnostic sensitivity was significantly higher with mpMRI than with simplified bpMRI (P < 0.001 to P = 0.035); and although specificity was also higher with mpMRI than with simplified bpMRI for radiologist B and radiologist C, it was statistically significant only for radiologist B (P = 0.011, P = 0.359, respectively). On the contrary, for radiologist A, specificity was higher with simplified bpMRI than with mpMRI (P = 0.001). The area under the receiver operating characteristic curve (AUC) was significantly higher for mpMRI than for simplified bpMRI except for radiologist A (radiologist A: 0.903 vs 0.913, P = 0.1542; radiologist B: 0.861 vs 0.834 P = 0.0013; and radiologist C: 0.884 vs 0.848, P = 0.0003). Interobserver reliability of PI-RADS v2.1 showed good agreement for both simplified bpMRI (kappa = 0.665) and mpMRI (kappa = 0.739). CONCLUSION: Although the detection of csPCa with simplified bpMRI was comparatively lower than that with mpMRI, the diagnostic performance was still high in simplified bpMRI. Our data justify using mpMRI outperforms simplified bpMRI for prostate cancer screening and imply simplified bpMRI as a potential screening tool.

The value of luteinizing hormone basal values and sex hormone-binding globulin for early diagnosis of rapidly progressive central precocious puberty.

Objective: This study aimed to investigate the diagnostic value of luteinizing hormone (LH) basal values and sex hormone-binding globulin (SHBG) for rapidly progressive central precocious puberty (RP-CPP). Methods: A total of 121 girls presenting with secondary sexual characteristics were selected from the Department of Pediatric Endocrinology, Lianyungang Clinical Medical College of Nanjing Medical University, from May 2021 to June 2023. The children were followed up for 6 months and were divided into three groups: RP-CPP group (n=40), slowly progressive central precocious puberty (SP-CPP) group (n=40), and premature thelarche (PT) group (n=41). The differences in LH basal values and SHBG among girls in the three groups were compared. ROC curves were drawn to analyze the value of LH basal values and SHBG in identifying RP-CPP. Results: Significant differences were observed in age, height, predicted adult height (PAH), weight, body mass index (BMI), bone age (BA), BA-chronological age (CA), LH basal, LH peak, FSH basal, LH peak/FSH peak, estradiol (E2), testosterone, and SHBG levels between the RP-CPP group and the SP-CPP and PT groups (P < 0.05). The LH basal value in the RP-CPP group was higher than that in the SP-CPP group and the PT group, while SHBG levels were lower than in the latter two groups, and these differences were statistically significant (P < 0.05). When the LH basal value was ≥0.58 IU/L and SHBG was ≤58.79 nmol/L, the sensitivity for diagnosing RP-CPP was 77.5% and 67.5%, and the specificity was 66.7% and 74.1%. Conclusion: Detection of basal LH and SHBG levels allows for early diagnosis of the progression of central precocious puberty.

Exosomal RNA Expression Profiles and Their Prediction Performance in Patients With Gestational Diabetes Mellitus and Macrosomia.

Introduction: Exosomes are cell-derived vesicles that are present in many biological fluids. Exosomal RNAs in cord blood may allow intercellular communication between mother and fetus. We aimed to establish exosomal RNA expression profiles in cord blood from patients with gestational diabetes mellitus and macrosomia (GDM-M) and evaluate their prediction performance. Methods: We used microarray technology to establish the differential messenger RNA (mRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA) expression profiles in cord blood exosomes from 3 patients with GDM-M compared with 3 patients with GDM and normal neonatal weight, followed by qPCR validation in an additional 40 patients with GDM. Logistic regression, receiver operating characteristic (ROC) curves, and graphical nomogram were applied to evaluate the performance of exosomal RNA (in peripheral blood) in macrosomia prediction. Results: A total of 98 mRNAs, 372 lncRNAs, and 452 circRNAs were differentially expressed in cord blood exosomes from patients with GDM-M. Pathway analysis based on screening data showed that the differential genes were associated with Phosphatidylinositol 3'-kinase (PI3acK)-Akt signaling pathway, Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway, Transforming growth factor (TGF)-beta signaling pathway, insulin resistance, glycerolipid metabolism, fatty acid degradation, and mammalian target of rapamycin (mTOR) signaling pathway. After validation by qPCR, the expressions of GDF3, PROM1, AC006064.4, lnc-HPS6-1:1, and circ_0014635 were significantly increased and the expression of lnc-ZFHX3-7:1 was significantly decreased in cord blood exosomes of an additional 20 patients with GDM-M. The risk prediction performance of the expression of these validated genes (in peripheral blood exosomes) for GDM-related macrosomia was also evaluated. Only GDF3 expression and AC006064.4 expression showed well prediction performance [area under the curve (AUC) = 0.78 and 0.74, respectively]. Excitingly, the model including maternal age, fasting plasma glucose, 2-h plasma glucose, GDF3 expression, and AC006064.4 expression in peripheral blood exosomes had better prediction performance with an AUC of 0.86 (95% CI = 0.75-0.97). Conclusion: These results showed that exosomal RNAs are aberrantly expressed in the cord blood of patients with GDM-M and highlighted the importance of exosomal RNAs in peripheral blood for GDM-M prediction.

Association of maternal serum 25-hydroxyvitamin D concentrations with risk of preeclampsia: a nested case-control study and meta-analysis.

OBJECTIVES: Whether the maternal vitamin D deficiency is associated with preeclampsia is still an argument. We aimed to assess the association between maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations and risk of preeclampsia in a Chinese population and systematically evaluate published evidence on this association. METHODS: We conducted a nested case-control study involving 122 pregnant women with preeclampsia and 488 pregnant women whose blood pressure was within the normal range (as controls). For further meta-analysis, 20 studies and our study were included for the final pooled analysis, involving 39,031 participants and 3305 preeclampsia cases with various ethnicities. RESULTS: The results showed that 65.6% of women with preeclampsia had serum 25(OH)D concentrations <50.0 nmol L-1 compared with 55.3% of women in controls. The 25(OH)D concentrations were significantly lower in women with preeclampsia than controls [Median (IQR), women with preeclampsia versus controls: 43.3 (35.5, 55.2) versus 47.5 (37.6, 60.4) nmol L-1, p = .014]. For women with 25(OH)D concentrations <50.0 nmol L-1, they had a 65% increase in preeclampsia risk (95% CI = 1.02-2.69), as compared with women with 25(OH)D concentrations from 50.0 to 74.9 nmol L-1. Further, meta-analysis showed that low 25(OH)D concentrations were associated with a significantly increased risk of preeclampsia by 62% (pooled OR = 1.62, 95%CI = 1.36-1.94), and the risk effect of low 25(OH)D concentrations existed in most subgroups. CONCLUSIONS: Low 25(OH)D concentration in pregnancy was significantly associated with preeclampsia risk, and it may serve as biomarkers for the surveillance of high-risk pregnant women.

The role and possible mechanism of lncRNA AC092159.2 in modulating adipocyte differentiation.

Obesity is a major risk factor for metabolic diseases, while adipocyte differentiation is closely related to obesity occurrence. Long noncoding RNAs (lncRNAs) are a unique class of transcripts in regulation of various biological processes. Using lncRNA microarray, we found lncRNA AC092159.2 was highly expressed in differentiated HPA-v and located ~247 bp upstream of the TMEM18, which was associated with BMI and obesity. We aimed to explore the role of AC092159.2 in adipogenesis and the underlying mechanisms. The effects of AC092159.2 gain- and loss-of-function on HPA-v adipogenesis were determined with lentivirus and siRNA-mediated cell transduction, respectively. Lipid accumulation was evaluated by oil red O staining; the expression of AC092159.2, TMEM18 and several adipogenesis makers in HPA-v were analyzed by qPCR/Western blot. We found that the expression of AC092159.2 gradually increased during HPA-v differentiation, and its expression in omental adipose tissue was positively related with BMI among 48 human subjects. Overexpression of AC092159.2 promoted adipocytes differentiation while knockdown of it led to an adipogenic defect. Moreover, the expression of AC092159.2 and TMEM18 were positively correlated during adipogenic differentiation. AC092159.2 overexpression boosted TMEM18 expression while AC092159.2 knockdown restrained TMEM18 expression. Further rescue experiments showed that TMEM18 knockdown partially restrained adipogenic differentiation in AC092159.2 overexpressed HPA-v and adipogenic defect caused by AC092159.2 knockdown could be rescued by TMEM18 overexpression. Luciferase reporter assays revealed that AC092159.2 had a transcriptional activation effect on TMEM18. We concluded that lncRNA AC092159.2 promoted human adipocytes differentiation possibly by regulating TMEM18.

Genetic factors associated with risk of metabolic syndrome and hepatocellular carcinoma.

Although the metabolic syndrome is a commonplace topic, its potential threats to public health is a problem that cannot be neglected. As the living conditions improved significantly over the past few years, the morbidity of metabolic syndrome has also steadily risen, and the onset age is becoming younger. The hepatocellular carcinoma (HCC), is one of the most prevalent life-threatening human cancers worldwide, incidence of which is also on the rise, gradually occupied the top of the list associated with metabolic syndrome related complication. Despite the advanced improvement of HCC management, the lifestyle, environmental factors, obesity, hepatitis B virus (HBV) infection have been recognized as risk factors for the development of liver cancer. In recent years, genetic studies, especially the genome-wide association studies (GWASs) were widely performed, a new era of the human genome research was created, which has significantly promoted the study of complex disease genetics. These progresses have contributed to the discovery of abundant number of genomic loci convincingly linked with complex metabolic feature and HCC. In this review, we briefly summarize the association between metabolic syndrome and HCC, focusing on the genetic factors contributed to metabolic syndrome and HCC.