Investigation Into the Predictive Potential of Three-Dimensional Ultrasonographic Placental Volume and Vascular Indices in Gestational Diabetes Mellitus

BackgroundThe use of ultrasonography in pregnancies complicated with gestational diabetes mellitus (GDM) can vary according to clinical practice. This study aims to compare the changes of placental volume (PV) and vascular indices measured by three-dimensional (3D) Power Doppler between pregnant women with and without GDM.Materials and MethodsThis was a prospective study of singleton pregnancies who took the early nuchal translucency examination from January 2018 to September 2019. Data on PV and vascular indices including vascularization index (VI), flow index (FI), and vascularization flow index (VFI) between pregnant women with and without GDM were measured by 3D Power Doppler ultrasound machine. Univariate and multivariate logistic regression determined the association between risk factors and GDM. Receiver operating characteristic (ROC) and area under the ROC curve (AUC) were applied to evaluate the diagnostic value of different parameters for GDM.ResultsOf the 141 pregnant women enrolled, 35 developed GDM and 106 did not. The maternal age and gravida in the GDM group were significantly higher than that in the non-GDM group. The PV, VI, FI, and VFI in the GDM group were significantly lower than that in the non-GDM group. There were no significant differences in other clinical parameters between the two groups. After adjustments in multivariate logistic regression analysis, significant differences were observed in VI [odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.951–1.002], FI (OR = 0.93, 955 CI: 0.86–1.00), and VFI (OR = 0.67, 95% CI = 0.52–0.87). ROC analysis indicated that the combination of maternal age, gravida, PV, and VFI was more accurate as a marker for detecting GDM than the PV, VI, FI, or VFI alone.ConclusionsThe 3D ultrasonography results suggest that PV and vascular indices (VI, FI, and VFI) during the first trimester may serve as potential markers for GDM diagnosis. The combination of maternal age, gravida, and sonographic markers may have good diagnostic values for GDM, which should be confirmed by further investigations

Mechanisms of Triptolide-Induced Hepatotoxicity and Protective Effect of Combined Use of Isoliquiritigenin: Possible Roles of Nrf2 and Hepatic Transporters

Triptolide (TP), the main bioactive component of Tripterygium wilfordii Hook F, can cause severe hepatotoxicity. Isoliquiritigenin (ISL) has been reported to be able to protect against TP-induced liver injury, but the mechanisms are not fully elucidated. This study aims to explore the role of nuclear transcription factor E2-related factor 2 (Nrf2) and hepatic transporters in TP-induced hepatotoxicity and the reversal protective effect of ISL. TP treatment caused both cytotoxicity in L02 hepatocytes and acute liver injury in mice. Particularly, TP led to the disorder of bile acid (BA) profiles in mice livers. Combined treatment of TP with ISL effectively alleviated TP-induced hepatotoxicity. Furthermore, ISL pretreatment enhanced Nrf2 expressions and nuclear accumulations and its downstream NAD(P)H: quinine oxidoreductase 1 (NQO1) expression. Expressions of hepatic P-gp, MRP2, MRP4, bile salt export pump, and OATP2 were also induced. In addition, in vitro transport assays identified that neither was TP exported by MRP2, OATP1B1, or OATP1B3, nor did TP influence the transport activities of P-gp or MRP2. All these results indicate that ISL may reduce the hepatic oxidative stress and hepatic accumulations of both endogenous BAs and exogenous TP as well as its metabolites by enhancing the expressions of Nrf2, NQO1, and hepatic influx and efflux transporters. Effects of TP on hepatic transporters are mainly at the transcriptional levels, and changes of hepatic BA profiles are very important in the mechanisms of TP-induced hepatotoxicity

SHMT2 Promotes Gastric Cancer Development through Regulation of HIF1α/VEGF/STAT3 Signaling

The metabolic enzymes involved in one-carbon metabolism are closely associated with tumor progression and could be potential targets for cancer therapy. Recent studies showed that serine hydroxymethyltransferase 2 (SHMT2), a crucial enzyme in the one-carbon metabolic pathway, plays a key role in tumor proliferation and development. However, the precise role and function of SHMT2 in gastric cancer (GC) remain poorly understood. In this study, we presented evidence that SHMT2 was necessary for hypoxia-inducible factor-1α (HIF1α) stability and contributed to GC cells’ hypoxic adaptation. The analysis of datasets retrieved from The Cancer Genome Atlas and the experimentation with human cell lines revealed a marked increase in SHMT2 expression in GC. The SHMT2 knockdown in MGC803, SGC7901, and HGC27 cell lines inhibited cell proliferation, colony formation, invasion, and migration. Notably, SHMT2 depletion disrupted redox homeostasis and caused glycolytic function loss in GC cells under hypoxic circumstances. Mechanistically, we discovered SHMT2 modulated HIF1α stability, which acted as a master regulator of hypoxia-inducible genes under hypoxic conditions. This, in turn, regulated the downstream VEGF and STAT3 pathways. The in vivo xenograft experiments showed that SHMT2 knockdown markedly reduced GC growth. Our results elucidate the novel function of SHMT2 in stabilizing HIF1α under hypoxic conditions, thus providing a potential therapeutic strategy for GC treatment

ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cells

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with an immunosuppressive tumor microenvironment (TME). In this environment, myeloid cells, such as myeloid-derived suppressor cells (MDSCs), play a pivotal role in suppressing antitumor immunity. Lipometabolism is closely related to the function of myeloid cells. Here, our study reports that acetyl-CoA acetyltransferase 1 (ACAT1), the key enzyme of fatty acid oxidation (FAO) and ketogenesis, is significantly downregulated in the MDSCs infiltrated in GBM patients. To investigate the effects of ACAT1 on myeloid cells, we generated mice with myeloid-specific (LyzM-cre) depletion of ACAT1. The results show that these mice exhibited a remarkable accumulation of MDSCs and increased tumor progression both ectopically and orthotopically. The mechanism behind this effect is elevated secretion of C–X–C motif ligand 1 (CXCL1) of macrophages (Mφ). Overall, our findings demonstrate that ACAT1 could serve as a promising drug target for GBM by regulating the function of MDSCs in the TME

A risk score for predicting in-stent restenosis in patients with premature acute myocardial infarction undergoing percutaneous coronary intervention with drug-eluting stent

Background: This study aimed at developing and validating a risk score to predict in-stent restenosis (ISR) in patients with premature acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES). Methods: This was a two-center retrospective study. A total of 2185 patients firstly diagnosed with premature AMI (age ≥18 years and <55 years in men, <65 years in women) from Xinjiang cohort were retrospectively analyzed. After filtering by exclusion criteria, patients were randomly divided into training cohort (n = 434) and internal validation cohort (n = 186) at a 7:3 ratio. Several candidate variables associated with ISR in the training cohort were assessed by the least absolute shrinkage and selection operator and logistic regression analysis. The ISR risk nomogram score based on the superior predictors was finally developed, and then validated in the internal validation cohort and in an independent Chengdu external validation cohort (n = 192). The higher total nomogram score, the greater the ISR risk. Results: The eight variables in the final risk nomogram score, cardiovascular-kidney-metabolic (CKM) score included age, diabetes mellitus (DM), body mass index (BMI), systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDLC), estimated glomerular filtration rate (eGFR), stent in left anterior descending coronary artery, minimum stent diameter <3 mm. The areas under the curve (AUC) and C-statistics [training cohort: 0.834 (95%CI: 0.787 to 0.882); internal validation cohort: 0.852 (95%CI: 0.784 to 0.921); Chengdu external validation cohort: 0.787 (95%CI: 0.692 to 0.882), respectively)] demonstrated the good discrimination of the CKM score. The Hosmer-Lemeshow test (χ2 = 7.86, P = 0.448; χ2 = 5.17, P = 0.740; χ2 = 6.35, P = 0.608, respectively) and the calibration curve confirmed the good calibration of the CKM score. Decision curve analysis (DCA) testified the clinical net benefit of the CKM score in the training and validation cohort. Conclusion: This study provided a well-developed and validated risk nomogram score, the CKM score to predict ISR in patients with premature AMI undergoing PCI with DES. Given that these variables are readily available and practical, the CKM score should be widely adopted for individualized assessment and management of premature AMI

Comparison of positive attitudes (Yes response) towards HBV, stratified by hospital.

<p>Comparison of positive attitudes (Yes response) towards HBV, stratified by hospital.</p

Knowledge of and attitudes towards hepatitis B and its transmission from mother to child among pregnant women in Guangdong Province, China

<div><p>Background</p><p>Hepatitis B virus (HBV) infection remains a serious public health problem worldwide. Mother-to-child transmission (MTCT) of HBV is the major mode of transmission in HBV-endemic areas, including China, where little is known about pregnant women’s knowledge of and attitudes towards HBV infection and MTCT.</p><p>Methods</p><p>A cross-sectional survey, conducted in pregnant women in Guangdong Province, China, measured HBV knowledge and attitudes using a questionnaire, at one tertiary and two rural hospitals.</p><p>Results</p><p>The total response rate was 94.5% (737/780). Of the 11 knowledge questions, the mean score was 6.73 ± 3.04 (mean ± SD). Most pertinent to preventing MTCT, 53.3% of the respondents did not know that HBV can be transmitted through unprotected sexual intercourse and nearly 20% did not know that HBV can be transmitted from mother to infant. The results of the four attitude questions was better with 83% and 85% being willing to be screened for HBV and let their baby receive HBV vaccine and HBIg, respectively. However, only 16.5% of respondents agreed that they would be willing to take drugs that are known not to harm the fetus to prevent MTCT of HBV. In multivariable analysis, higher education level was associated with better knowledge and attitude scores.</p><p>Conclusions</p><p>Knowledge about HBV among pregnant women was poor and needs to be improved to prevent MTCT of HBV. Health education needs to be directed towards pregnant mothers, particularly less educated mothers, in high HBV endemicity settings.</p></div

Comparison of positive attitudes (Yes response) towards HBV, stratified by hospital.

<p>Comparison of positive attitudes (Yes response) towards HBV, stratified by hospital.</p