Hemoglobin within normal range is negatively related to hemoglobin A1c in a nondiabetic American population aged 16 years and older.

BACKGROUND: Protein glycosylated hemoglobin, hemoglobin A1c (HbA1c) binds hemoglobin (Hb) in red blood cells to blood glucose. However, the relationship between Hb and HbA1c remains unclear. AIM: To elucidate their relationship in a nondiabetic population aged ≥ 16 years in the United States, using data from the 1999-2018 National Health and Nutrition Examination Survey. METHODS: This study was based on data from 44560 adults aged ≥ 16 years, excluding those with diabetes. The relationship was estimated using a multivariate regression. We also used piecewise linear regression for subgroup analysis based on age and sex stratification and analysis of the threshold effects of Hb on HbA1c. RESULTS: Hb and HbA1c levels were negatively correlated in the unadjusted model (ß = -0.01; 95%CI: -0.01, -0.01). The correlation was significantly negative when the regression model was minimally regulated and stratified by age and sex, and remained negative when the model was further regulated (more than 10%) to identify covariates with the HbA1c level influence estimates. In subgroup analyses based on age and sex stratification, the association remained negative when the covariates were controlled. A nonlinear relationship was observed between them when the Hb levels reached the tipping point (13.2 g/dL) (adjusted odds ratio, -0.04; 95%CI: -0.05, -0.03) and when the Hb levels exceeded 13.2 g/dL (adjusted odds ratio, -0.10; 95%CI: -0.10, -0.09). CONCLUSION: Our study shows that normal Hb levels are negatively correlated with HbA1c in nondiabetic Americans aged ≥ 16 years.

Long Noncoding RNA MALAT1 Regulates Hepatocellular Carcinoma Growth Under Hypoxia via Sponging MicroRNA-200a.

PURPOSE: Hepatocellular carcinoma (HCC) is a common cancer worldwide. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long noncoding RNA (lncRNA), has been reported to be aberrantly expressed in hypoxic cancer cells. MALAT1 plays a significant role in many malignancies, including HCC. The aim of this study was to explore the role of MALAT1 in hypoxic HCC cells and its underlying regulatory mechanism. MATERIALS AND METHODS: Quantitative reverse transcription PCR (qRT-PCR) assay was performed to detect the mRNA levels of MALAT1 and microRNA-200a (miR-200a) in HCC cells. Cell invasion and migration ability were evaluated by Transwell assay. Starbase v2.0 and luciferase reporter assay were employed to identify the association between MALAT1 and miR-200a. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry, respectively. RESULTS: MALAT1 levels were significantly upregulated in HCC cells under hypoxia. Hypoxia promoted proliferation, migration, and invasion, and blocked apoptosis in Hep3B cells, which were weakened by knockdown of MALAT1. Starbase v2.0 showed that MALAT1 and miR-200a have a complementarity region, and luciferase reporter assay verified that MALAT1 interacted with miR-200a in Hep3B cells. Moreover, MALAT1 negatively regulated the expression of miR-200a. miR-200a levels were dramatically downregulated in HCC cells under hypoxia. Upregulation of miR-200a inhibited proliferation, migration, and invasion, and induced apoptosis in Hep3B cells under hypoxia. Interestingly, downregulation of miR-200a partially reversed the tumor-suppressive effect of knockdown of MALAT1 on Hep3B cells in hypoxic condition. CONCLUSION: LncRNA MALAT1 was involved in proliferation, migration, invasion, and apoptosis by interacting with miR-200a in hypoxic Hep3B cells, revealing a new mechanism of MALAT1 involved in hypoxic HCC progression.

Combination of the CYP2C19 metabolizer and the GRACE risk score better predicts the long-term major adverse cardiac events in acute coronary syndrome undergoing percutaneous coronary intervention.

INTRODUCTION: Both Global Registry of Acute Coronary Events (GRACE) risk score and CYP2C19 metabolizer status can independently predict major adverse cardiac events (MACEs) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We investigated whether their combination could better predict MACE occurrence in patients with ACS undergoing PCI. MATERIALS AND METHODS: This retrospective cohort study included 548 consecutive patients with ACS undergoing PCI. A cumulative MACE curve was calculated using the Kaplan-Meier method. Multivariate Cox regression was used to identify MACE predictors. The predictive value of GRACE risk score alone and CYP2C19 metabolizer status was estimated by the area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: In a median of 28.58 months, 17 patients (3%) were lost to follow-up, and 62 (11.3%) experienced MACEs. Multivariate Cox regression analysis showed that both GRACE score and CYP2C19 metabolizer status were independent MACE predictors (hazard ratio 1.019, 95% CI 1.011-1.027, p < 0.001; hazard ratio 2.383, 95% CI 1.601-3.547, p < 0.001, respectively). Kaplan-Meier analysis showed that CYP2C19 PM increased the MACE risk (log rank test = 10.848, p = 0.004). The GRACE score adjustment by CYP2C19 metabolizer status enhanced the predictive value (AUC increased from 0.682 for GRACE score alone to 0.731 for GRACE score plus CYP2C19 metabolizer). This result was further verified by IDI and NRI. CONCLUSIONS: CYP2C19 metabolizer status and GRACE score are readily available predictive approaches for MACEs, and their combination derives a more accurate long-term MACE prediction in clopidogrel-treated patients with ACS undergoing PCI.