Objective:To investigate the value of the preoperative peripheral blood lymphocyte-to-monocyte ratio (LMR) in evaluating the prognosis of patients with resectable gastric and esophageal neuroendocrine carcinoma.Methods:The clinical and pathological data of 49 patients with gastric and esophageal neuroendocrine carcinoma in the Third Affiliated Hospital of Soochow University From March 2013 to December 2018 was retrospectively analyzed. The best cut-off value of the preoperative LMR was determined by using the receiver operating characteristic curve (ROC), and patients were divided into low LMR group (LMR<3.587, 24 cases) and high LMR group (LMR≥3.587, 25 cases). The clinicopathological characteristics and overall survival (OS) of patients in low and high LMR groups were compared, and the factors affecting the prognosis of patients with gastric and esophageal neuroendocrine carcinoma were explored.Results:The LMR was related to the neutrophil-to-lymphocyte ratio (NLR) ( χ2 = 22.329, P < 0.01) and the prognostic nutritional index (PNI) ( χ2 = 5.384, P = 0.020). The LMR was positively correlated with the PNI ( r = 0.443, P = 0.001) and negatively correlated with the NLR ( r = -0.362, P = 0.011), while the gender, age, tumor maximum diameter, lymph node involvement, T staging, distant metastasis, vascular tumor thrombus, tumor site, treatment method, C-reactive protein-to-albumin ratio (CRP/Alb), and modified Glasgow prognostic score (mGPS) were irrelevant with LMR (all P > 0.05). The median OS time of patients in high and low LMR groups was unreached and 13.1 months (95% CI 5.532-20.735 months), respectively, the low LMR group had a worse prognosis, and the difference was statistically significant ( χ2 = 8.685, P = 0.003). Multivariate analysis showed that the lymph node staging, treatment method and LMR were independent influencing factors of OS (all P < 0.05). Conclusion:Preoperative LMR is a simple and repeatable biological index, which can be considered as an independent influencing factor for the prognosis of patients with gastric and esophageal neuroendocrine carcinoma.

OBJECTIVETo explore the correlation between methylation of insulin-like growth factor 1 (IGF-1) gene promoter and its placenta-specific expression and fetal macrosoma.

METHODSOne hundred twenty nine healthy pregnant women were recruited between April 2011 and March 2012. Baseline data were collected with self-report questionnaires. Real-time quantitative PCR was used to determine the expression of IGF-1 mRNA in the placenta. Methylation level of the IGF 1 gene was determined with matrix-assisted laser desorption/ionization-time of flight mass spectrometry.

RESULTSThe expression of IGF-1 in placenta and its methylation level showed no significant difference between macrosomic fetuses and controls. No linear correlation was found between IGF-1 mRNA expression and methylation level of IGF-1 promoter (r=0.128, P=0.295). IGF-1 promoter region in placenta showed a hypomethylation status. However, a positive correlation was found between IGF-1 expression and birth weight below 4260 g (r=0.264, P=0.022). The expression of IGF-1 mRNA was significantly higher in those with a birth weight below 4260 g, which suggested that placental IGF-1 expression may contribute to increased birth weight. In regard to fetal overgrowth, however, there seemed to be a negative correlation in which placental IGF-1 expression was downregulated to limit fetal overgrowth.

CONCLUSIONNo linear correlation was found between placental IGF-1 expression and methylation level of IGF-1 promoter with a hypomethylation status. The contribution of placental IGF-1 expression to birth weight is bidirectional. Increased expression seems to promote fetal growth, while decreased expressions may curb overgrowth, therefore control fetal growth in a relatively normal range.

Birth Weight ; DNA Methylation ; Female ; Fetal Macrosomia ; genetics ; Humans ; Infant, Newborn ; Insulin-Like Growth Factor I ; genetics ; Placenta ; metabolism ; Pregnancy ; Promoter Regions, Genetic ; RNA, Messenger ; analysis

Background::We previously reported that activation of the cell cycle in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enhances their remuscularization capacity after human cardiac muscle patch transplantation in infarcted mouse hearts. Herein, we sought to identify the effect of magnesium lithospermate B (MLB) on hiPSC-CMs during myocardial repair using a myocardial infarction (MI) mouse model.Methods::In C57BL/6 mice, MI was surgically induced by ligating the left anterior descending coronary artery. The mice were randomly divided into five groups ( n = 10 per group); a MI group (treated with phosphate-buffered saline only), a hiPSC-CMs group, a MLB group, a hiPSC-CMs + MLB group, and a Sham operation group. Cardiac function and MLB therapeutic efficacy were evaluated by echocardiography and histochemical staining 4 weeks after surgery. To identify the associated mechanism, nuclear factor (NF)-κB p65 and intercellular cell adhesion molecule-1 (ICAM1) signals, cell adhesion ability, generation of reactive oxygen species, and rates of apoptosis were detected in human umbilical vein endothelial cells (HUVECs) and hiPSC-CMs. Results::After 4 weeks of transplantation, the number of cells that engrafted in the hiPSC-CMs + MLB group was about five times higher than those in the hiPSC-CMs group. Additionally, MLB treatment significantly reduced tohoku hospital pediatrics-1 (THP-1) cell adhesion, ICAM1 expression, NF-κB nuclear translocation, reactive oxygen species production, NF-κB p65 phosphorylation, and cell apoptosis in HUVECs cultured under hypoxia. Similarly, treatment with MLB significantly inhibited the apoptosis of hiPSC-CMs via enhancing signal transducer and activator of transcription 3 (STAT3) phosphorylation and B-cell lymphoma-2 (BCL2) expression, promoting STAT3 nuclear translocation, and downregulating BCL2-Associated X, dual specificity phosphatase 2 (DUSP2), and cleaved-caspase-3 expression under hypoxia. Furthermore, MLB significantly suppressed the production of malondialdehyde and lactate dehydrogenase and the reduction in glutathione content induced by hypoxia in both HUVECs and hiPSC-CMs in vitro. Conclusions::MLB significantly enhanced the potential of hiPSC-CMs in repairing injured myocardium by improving endothelial cell function via the NF-κB/ICAM1 pathway and inhibiting hiPSC-CMs apoptosis via the DUSP2/STAT3 pathway.