Single-Cell RNA Sequencing of hESC-Derived 3D Retinal Organoids Reveals Novel Genes Regulating RPC Commitment in Early Human Retinogenesis.

The development of the mammalian retina is a complicated process involving the generation of distinct types of neurons from retinal progenitor cells (RPCs) in a spatiotemporal-specific manner. The progression of RPCs during retinogenesis includes RPC proliferation, cell-fate commitment, and specific neuronal differentiation. In this study, by performing single-cell RNA sequencing of cells isolated from human embryonic stem cell (hESC)-derived 3D retinal organoids, we successfully deconstructed the temporal progression of RPCs during early human retinogenesis. We identified two distinctive subtypes of RPCs with unique molecular profiles, namely multipotent RPCs and neurogenic RPCs. We found that genes related to the Notch and Wnt signaling pathways, as well as chromatin remodeling, were dynamically regulated during RPC commitment. Interestingly, our analysis identified that CCND1, a G1-phase cell-cycle regulator, was coexpressed with ASCL1 in a cell-cycle-independent manner. Temporally controlled overexpression of CCND1 in retinal organoids demonstrated a role for CCND1 in promoting early retinal neurogenesis. Together, our results revealed critical pathways and novel genes in early retinogenesis of humans

Downregulation of Death-associated Protein Kinase 3 and Caspase-3 Correlate to the Progression and Poor Prognosis of Gliomas

Aim: To investigate the role of death-associated protein kinase 3 (DAPK3) and activated caspase-3 in glioma condition. Methods: Immunohistochemical staining for DAPK3 and activated caspase-3 was performed on 136 paraffin-embedded glioma samples and 15 normal brain tissues, and the relationship between their expression levels and clinico-pathological features of glioma was statistically analyzed. Univariate and multivariate analyses were used to evaluate their prognostic value and patients′ survival. Results: The expression of both DAPK3 and activated caspase-3 was found suppressed in glioma tissues (P = 0.001 and P = 0.043). Further, DAPK3 and activated caspase-3 expression were markedly correlated with World Health Organization (WHO) Grading (I-II vs. III-IV) of the glioma condition (P = 0.002 and P < 0.001). A significantly positive correlation was observed between DAPK3 and activated caspase-3 expression (Spearman′s correlation coefficient = 0.706; P < 0.001). Univariate analysis revealed that both DAPK3 and activated caspase-3 were significantly associated with the overall survival of glioma patients (P < 0.001 and P < 0.001). In addition, multivariate analysis demonstrated that only DAPK3 and activated caspase-3 protein levels, but not WHO grading, significantly correlated with patients′ survival (P = 0.008 and P = 0.042). Conclusion: Downregulation of DAPK3 and activated caspase-3 is strongly associated with the clinical progression and poor prognosis of glioma, suggesting their use as a reliable clinical predictor

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Central aortic systolic blood pressure can predict prolonged QTc duration better than brachial artery systolic blood pressure in rural community residents

Objectives: Previous studies have suggested that prolonged electrocardiogram QTc duration was independent risk factor for both increased cardiovascular and all-cause mortality, but there was no dating about the relationship between central aortic systolic blood pressure (CASP) and QTc duration. The aim of this study was to analyze the relationship between CASP and QTc duration, and assess whether CASP can predict prolonged QTc duration more than BSBP. Methods: A total of 500 patients were enrolled in this study, central and brachial aortic blood pressure and electrocardiogram QTc duration were measured. Pearson correlation was assessed for determining the associations of QTc duration with clinical conditions. Multivariate logistic regression analyses were performed to determine the independent predictor of prolonged QTc duration. Receiver operating characteristic (ROC) curve was used to evaluate the utility of blood pressure for prolonged QTc duration. Results: We found QTc durations were significantly positive with CASP (r = 0.308, p < 0.001), BSBP (r = 0.227, p < 0.001), and age (r = 0.154, p = 0.010), but negatively related to heart rate (r = −440, p < 0.001). A multiple logistic regression analysis demonstrated that the CASP was an independent determinant of prolonged QTc (OR = 1.648; 95%CI: 1.032, 2.101; p < 0.001). CASP had a better predictive value for prolonged QTc duration than (AUC: 0.771 vs. 0.646, p < 0.001) BSBP. Conclusion: Our results suggested that the non-invasive CASP is independently correlated with QTc duration, and CASP can predict prolonged QTc duration more than BSBP

Clinical Analysis of Venetoclax Combined with Azacitidinein Hig-risk Myelodysplastic Syndrome

Objective To investigate the efficacy and safety of Venetoclax combined with Azacitidine in the treatment of high-risk myelodysplastic syndrome. Methods A total of 56 patients with high-risk myelodysplastic syndrome were enrolled from June 2019 to June 2022 in the Second Affiliated Hospital of Qiqihar Medical University.The patients were divided into a control group(n=30) and a study group(n=26) by simple random sampling.The control group received Azacitidine chemotherapy.The study group received Venetoclax combined with Azacitidine chemotherapy.The efficacy, adverse reactions, lactate dehydrogenase, β2 microglobulin, and folic acid were compared between the two groups. Results The overall response rate in the study group was higher than that in the control group(P0.05).After treatment, the serum levels of lactate dehydrogenase, β2 microglobulin and folic acid in the study group were all lower than those in the control group(P<0.05). Conclusion Venetoclax combined with Azacitidine can improve the therapeutic effect and safety on high-risk myelodysplastic syndrome

Single-Cell RNA Sequencing of hESC-Derived 3D Retinal Organoids Reveals Novel Genes Regulating RPC Commitment in Early Human Retinogenesis.

The development of the mammalian retina is a complicated process involving the generation of distinct types of neurons from retinal progenitor cells (RPCs) in a spatiotemporal-specific manner. The progression of RPCs during retinogenesis includes RPC proliferation, cell-fate commitment, and specific neuronal differentiation. In this study, by performing single-cell RNA sequencing of cells isolated from human embryonic stem cell (hESC)-derived 3D retinal organoids, we successfully deconstructed the temporal progression of RPCs during early human retinogenesis. We identified two distinctive subtypes of RPCs with unique molecular profiles, namely multipotent RPCs and neurogenic RPCs. We found that genes related to the Notch and Wnt signaling pathways, as well as chromatin remodeling, were dynamically regulated during RPC commitment. Interestingly, our analysis identified that CCND1, a G1-phase cell-cycle regulator, was coexpressed with ASCL1 in a cell-cycle-independent manner. Temporally controlled overexpression of CCND1 in retinal organoids demonstrated a role for CCND1 in promoting early retinal neurogenesis. Together, our results revealed critical pathways and novel genes in early retinogenesis of humans