Associations of ozone exposure with gestational diabetes mellitus and glucose homeostasis: Evidence from a birth cohort in Shanghai, China.

BACKGROUND: Associations between individual exposure to ozone (O3) and gestational diabetes mellitus (GDM) have rarely been investigated, and critical windows of O3 exposure for GDM have not been identified. OBJECTIVES: We aimed to explore the associations of gestational O3 exposure with GDM and glucose homeostasis as well as to identify the potential critical windows. METHODS: A total of 7834 pregnant women were included. Individual O3 exposure concentrations were evaluated using a high temporal-spatial resolution model. Each participant underwent an oral glucose tolerance test (OGTT) to screen for GDM between 24 and 28 gestational weeks. Multiple logistic and multiple linear regression models were used to estimate the associations of O3 with GDM risks and with blood glucose levels of OGTT, respectively. Distributed lag nonlinear models (DLNMs) were used to estimate the critical windows of O3 exposure for GDM. RESULTS: Nearly 13.29 % of participants developed GDM. After controlling for covariates, we observed increased GDM risks per IQR increment of O3 exposure in the first trimester (OR = 1.738, 95 % CI: 1.002-3.016) and the first two trimesters (OR = 1.576, 95 % CI: 1.005-2.473). Gestational O3 exposure was positively associated with increased fasting blood glucose (the first trimester: ß = 2.964, 95 % CI: 1.529-4.398; the first two trimesters: ß = 1.620, 95 % CI: 0.436-2.804) and 2 h blood glucose (the first trimester: ß = 6.569, 95 % CI: 1.775-11.363; the first two trimesters: ß = 6.839, 95 % CI: 2.896-10.782). We also observed a concentration-response relationship of gestational O3 exposure with GDM risk, as well as fasting and 2 h blood glucose levels. Additionally, 5-10 gestational weeks was identified as a critical window of O3 exposure for GDM development. CONCLUSION: In summary, we found that gestational O3 exposure disrupts glucose homeostasis and increases the risk of GDM in pregnant women. Furthermore, 5-10 gestational weeks could be a critical window for the effects of O3 exposure on GDM.

Thalamocortical Dysconnectivity In Lifelong Premature Ejaculation: A Functional MRI Study.

OBJECTIVES: To detect seed-based functional connectivity (FC) between various cortical sub-regions and the thalamus in lifelong premature ejaculation (LPE) patients and explore whether specific thalamocortical networks are significantly altered in PE patients compared to healthy controls (HCs) METHODS: Fifty non-medicated LPE patients and 40 age-matched HCs underwent a resting-state functional MRI. FC was adopted to identify specific thalamocortical connectivity between the thalamus and 6 cortical regions of interest (i.e., the motor cortex/supplementary motor, the prefrontal cortex, the temporal lobe, the posterior parietal cortex, the somatosensory cortex and the occipital lobe). In LPE patients, regression analysis was subsequently conducted to assess relationships of thalamocortical connectivity with the Premature Ejaculation Diagnostic Tool (PEDT) score and the Intravaginal Ejaculatory Latency Time (IELT). RESULTS: LPE patients had significantly decreased FC between the motor cortex and bilateral ventral thalamus, between the prefrontal cortex and left dorsomedial thalamus, as well as between the temporal cortex and bilateral ventromedial thalamus. In LPE patients, PEDT score was significantly positively associated with the thalamus-posterior parietal cortex FC, and negatively associated with the thalamus-temporal cortex FC, while IELT was positively associated with the thalamus-temporal cortex and thalamus-motor cortex FC. CONCLUSION: These results enrich the imaging evidence for the understanding of the neurobiological mechanisms and/or consequences of LPE.

PM2.5 exposure and maternal glucose metabolism in early pregnancy: Associations and potential mediation of 25-hydroxyvitamin D.

Gestational diabetes mellitus (GDM) has become a new global epidemic with a rapidly increasing prevalence. Previous studies have suggested that air pollution is associated with GDM risk, but the results are inconsistent, and mechanistic studies are limited. Based on a hospital-based cohort, a total of 6374 participants were included in this study. Individual daily PM2.5 exposure at a 1-km resolution was predicted using a full-spatiotemporal-coverage model. The results of multiple linear regression showed that glycated hemoglobin (HbA1c) was significantly associated with PM2.5 both in the 1-month preconception and in the first trimester of pregnancy. Additionally, HbA1c decreased 0.437% (95% CI: -0.629, -0.244) as the serum 25-hydroxyvitamin D (25(OH)D) increased by one interquartile range (IQR) (9.2 ng/ml). An IQR increase in PM2.5 exposure was also negatively associated with serum 25(OH)D (estimated change% and 95% CI: -7.249 (-9.054, -5.408) in the 1-month preconception and - 13.069 (-15.111, -10.979) in the first trimester of pregnancy). Mediation analysis showed that serum 25(OH)D status mediated the association between HbA1c and PM2.5 exposure both in the preconception and in the first trimester (mediated percent: 2.00% and 4.05% (Sobel p＜0.001), respectively). The result suggested a vicious cycle among PM2.5 exposure, lower serum VD status and a higher HbA1c. More studies are warranted since the protective effect of 25(OH)D against glucose disorders associated with air pollution in this study was limited.

An Internally Validated Nomogram for Predicting the Likelihood of Improvement of Clinical Global Impression in Patients With Lifelong Premature Ejaculation Treated With Dapoxetine.

BACKGROUND: Although the introduction of dapoxetine has ushered in a new era in the treatment of premature ejaculation, many patients with lifelong premature ejaculation (LPE) exhibit an unimproved clinical global impression even after treatment with dapoxetine. AIM: To investigate independent predictors of the improvement of Clinical Global Impression (iCGI) in patients with LPE treated with dapoxetine and develop a nomogram to predict a patient's likelihood of achieving iCGI. METHODS: Data of 243 patients with LPE diagnosed at Xijing Hospital (Xi'an, China) and Northwest Women's and Children's Hospital (Xi'an, China) from January 2019 to May 2020 were analyzed. Independent predictors of iCGI were identified, and a nomogram was developed using R software based on a multivariate logistic regression model. The predictive accuracy of the nomogram was measured using the area under the receiver operating characteristic curve. The nomogram was calibrated by comparing predictions with observations. MAIN OUTCOME MEASURES: The primary outcome was the patient-rated Clinical Global Impression of Change scale score after a 4-week course of dapoxetine treatment, which was collected via an online questionnaire. A Clinical Global Impression of Change score of ≥1 was defined as iCGI in this study. RESULTS: Patients with LPE with at least a bachelor's degree, a self-reported intravaginal ejaculation latency time of >1 minute, and an International Index of Erectile Function question 5 score of ≥3 were independent factors associated with achieving iCGI, whereas a Premature Ejaculation Diagnostic Tool question 1 score of ≥2 was an independent factor negatively associated with achieving iCGI. The predictive accuracy of the nomogram, which was developed by integrating all variables with independent predictive significance, was 0.710 (95% confidence interval: 0.702-0.718). In addition, the calibration plot demonstrated excellent agreement between predictions and observations. CLINICAL IMPLICATIONS: If the predictive performance of our nomogram is further proven in multiple external validations, it can be used to select suitable patients for dapoxetine treatment, thereby reducing the number of patients discontinuing treatment. STRENGTHS & LIMITATIONS: This study developed the first nomogram for predicting the likelihood of achieving iCGI in patients with LPE treated with dapoxetine. However, our nomogram was not externally validated using independent cohorts from other institutions. CONCLUSION: This study identified several independent predictors of iCGI in patients with LPE treated with dapoxetine. An effective nomogram was developed to predict their likelihood of achieving iCGI. External validations using data of Western patients with LPE are required to test the broader applicability of this Chinese patient-based tool. Hou G, Gao M, Zhang L, et al. An Internally Validated Nomogram for Predicting the Likelihood of Improvement of Clinical Global Impression in Patients With Lifelong Premature Ejaculation Treated With Dapoxetine. J Sex Med 2020;17:2341-2350.

Gestational weight gain targets during the second and third trimesters of pregnancy for women with gestational diabetes mellitus in China.

BACKGROUND/OBJECTIVES: Gestational weight gain (GWG) recommendations for pregnant women with gestational diabetes mellitus (GDM) in China are lacking. The present study aims to examine whether specific GWG targets for women with GDM can improve pregnancy outcomes in comparison with GWG according to the Institute of Medicine (IOM) targets. SUBJECTS/METHODS: Pregnant women diagnosed with GDM were selected from a retrospective cohort study of 8299 singleton pregnant women aged 18-45 years in 2012 (n = 1820). GWG ranges were calculated using a receiver operating characteristic (ROC) curve analysis (ROC targets) and the interquartile range (IR) method (the range from the 25th to 75th percentiles of the GWG among GDM women without adverse pregnancy outcomes, IR targets). RESULTS: The incidences of small for gestational age (SGA) births and pregnancy hypertension among women with GDM who gained weight within the ROC targets were lower than the incidences in women who gained weight within the IOM targets (SGA, 7.5% vs. 8.6%; pregnancy hypertension, 12.6% vs. 14.1%; both P < 0.05). GWG was associated with a risk of adverse pregnancy outcomes in the total sample (estimated values ranged from -2.95 to 2.08, all P < 0.05). No statistically significant associations between GWG and adverse pregnancy outcomes were observed in subgroups of pregnant women with appropriate GWGs according to the ROC, IR, and IOM targets. The ROC targets exhibited higher negative predictive values for adverse pregnancy outcomes than the IR and IOM targets. CONCLUSION: The ROC targets improved pregnancy outcomes and thus represent potential special GWG guidelines for women with GDM in China.

Development and evaluation of percentile distribution of body weight by gestational week as a tool for gestational weight management: a retrospective study based on hospital routine data.

OBJECTIVES: This study aimed to construct and validate smoothed gestational weight centile curves based on preconception weight status for Chinese pregnant women. DESIGN: A retrospective study based on hospital routine data SETTING: Hospital prenatal care. POPULATION: A cohort of pregnant Chinese women with preconception and gestational body weights without maternal or neonatal complications (sample 1, n=2992), and a non-selective independent sample (sample 2, n=7420), were selected from hospital routine data for curve construction and validation. STUDY DESIGN: Smoothed body weight centile curves for each gestational week were constructed using the LMS method in sample 1. Validation in sample 2 included analysis of agreement between predicted weight at the 38th week and observed values using the Bland-Altman Index. Predictions were also compared with international curves. RESULTS: Smoothed centile curves of gestational weight for the three preconception body mass index groups showed a similar non-linear increasing trend. The differences between predicted body weights and observed values were 0.66±1.58 kg, 0.14±1.61 kg and -0.54±2.06 kg in the underweight, normal weight and overweight groups, respectively. Bland-Altman Index values were 5.2%, 5.6% and 4.7% in the underweight, normal weight and overweight groups, respectively, with limits of agreement of -2.4~3.8 kg, -3.0~3.3 kg and -4.4~3.4 kg, respectively. These limits of agreement were narrower than those of available international curves. CONCLUSION: Body weight percentiles for gestational weeks 0-42 were proposed for underweight, normal weight or overweight Chinese women. These curves could constitute a useful tool for individualised gestational weight management by predicting body weight at a later gestation phase.

Clusters of week-specific maternal gestational weight gain pattern and their association with birthweight: an observational cohort study.

INTRODUCTION: Gestational weight gain varies widely among different populations, and an inappropriate gestational weight gain is associated with adverse pregnancy outcomes. We aimed to investigate week-specific serial changes in gestational weight gain in an urban Chinese population to derive clusters of gestational weight gain patterns and explore the impact of gestational weight gain patterns on birthweight. MATERIAL AND METHODS: This was an observational cohort study of 6130 women delivered at a university hospital in Shanghai, China. Pre-pregnancy bodyweight, height, week-specific and total gestational weight gain, pregnancy outcome and birthweight were extracted using electronic medical records. The association between gestational weight gain and gestational age was tested using linear regression, and week-specific reference percentiles for gestational weight gain were calculated. Hierarchical clustering was used to derive gestational weight gain clusters. Mean birthweight among the clusters was compared using Dunnet's test. RESULTS: We found a significant linear association between gestational weight gain and gestational age (r = 0.56; p < 0.00001). Seven distinct clusters of gestational weight gain pattern were identified. The birthweight significantly correlated with gestational weight gain (r = 0.28; p < 0.00001). Compared with the cluster that had normal gestational weight gain throughout the pregnancy, the mean birthweight among the clusters that had abnormal gestational weight gain (inadequate or excessive) in the third trimester was significantly different (p < 0.001), but those who achieved normal gestational weight gain (between 5 and 95 percentile) in the third-trimester had similar mean birthweight. CONCLUSION: Women with abnormal gestational weight gain before the third-trimester still had a fair chance of delivering a normal birthweight baby if their gestational weight gain was normal in the third-trimester, suggesting that interventions started even late in pregnancy may have a positive effect on fetal growth.

[Regulatory effect of Skp2 on the expression and transactivation of the androgen receptor in the progression of castration-resistant prostate cancer].

OBJECTIVE: To determine the expression of Skp2 in different prostate cancer (PCa) cell lines and tissues, and explore its influence on the androgen receptor (AR) signaling pathway and development of castration-resistant prostate cancer (CRPC). METHODS: The expression levels of Skp2 and AR in different PCa cell lines were detected by Western blot. After knockdown of Skp2 in the C4-2 and 22RV1 cells transfected with shRNA, the expressions of AR and P27 were determined and the activity of ARR3-Luc measured by dual-luciferase reporter gene assay following treatment with dihydrotestosterone (DHT). The expressions of AR and Skp2 in human naïve PCa or CRPC specimens were detected by immunohistochemical staining followed by analysis of their differences and correlation. RESULTS: The Skp2 protein expression level was significantly higher in the C4-2 or 22RV1 cells than in the LNCaP cells. DHT treatment increased the expression of Skp2 in the C4-2 cells, but knock-down of Skp2 significantly up-regulated the expression of the well-known downstream protein P27 and down-regulated that of AR. Consistently, DHT treatment increased the activity of ARR3-Luc, while knockdown of Skp2 remarkably decreased it in the C4-2 and 22RV1 cells (P < 0.05). In addition, significantly higher expressions of Skp2 and AR were observed in the CRPC than in the naïve specimens (P < 0.05), with a positive correlation between the two proteins (r = 0.658 1, P < 0.05). CONCLUSION: Skp2 can enhance the expression and transcription activity of the AR protein in CRPC cells or tissues and is promising to be a critical molecular therapeutic target.