Seven Glycolysis-Related Genes Predict the Prognosis of Patients With Pancreatic Cancer

ObjectivesTo identify the key glycolysis-related genes (GRGs) in the occurrence and development of pancreatic ductal carcinoma (PDAC), and to construct a glycolysis-related gene model for predicting the prognosis of PDAC patients.MethodologyPancreatic ductal carcinoma (PDAC) data and that of normal individuals were downloaded from the TCGA database and Genotype-Tissue Expression database, respectively. GSEA analysis of glycolysis-related pathways was then performed on PDAC data to identify significantly enriched GRGs. The genes were combined with other patient’s clinical information and used to construct a glycolysis-related gene model using cox regression analysis. The model was further evaluated using data from the validation group. Mutations in the model genes were subsequently identified using the cBioPortal. In the same line, the expression levels of glycolysis related model genes in PDAC were analyzed and verified using immunohistochemical images. Model prediction for PDAC patients with different clinical characteristics was then done and the relationship between gene expression level, clinical stage and prognosis further discussed. Finally, a nomogram map of the predictive model was constructed to evaluate the prognosis of patients with PDAC.ResultsGSEA results of the training set revealed that genes in the training set were significantly related to glycolysis pathway and iconic glycolysis pathway. There were 108 differentially expressed GRGs. Among them, 29 GRGs were closely related to prognosis based on clinical survival time. Risk regression analysis further revealed that there were seven significantly expressed glycolysis related genes. The genes were subsequently used to construct a predictive model. The model had an AUC value of more than 0.85. It was also significantly correlated with survival time. Further expression analysis revealed that CDK1, DSC2, ERO1A, MET, PYGL, and SLC35A3 were highly expressed in PDAC and CHST12 was highly expressed in normal pancreatic tissues. These results were confirmed using immunohistochemistry images of normal and diseases cells. The model could effectively evaluate the prognosis of PDAC patients with different clinical characteristics.ConclusionThe constructed glycolysis-related gene model effectively predicts the occurrence and development of PDAC. As such, it can be used as a prognostic marker to diagnose patients with PDAC

Efficacy of early prone or lateral positioning in patients with severe COVID-19: a single-center prospective cohort

Abstract Background Position intervention has been shown to improve oxygenation, but its role in non-invasively ventilated patients with severe COVID-19 has not been assessed. The objective of this study was to investigate the efficacy of early position intervention on non-invasively ventilated patients with severe COVID-19. Methods This was a single-center, prospective observational study in consecutive patients with severe COVID-19 managed in a provisional ICU at Renmin Hospital of Wuhan University from 31 January to 15 February 2020. Patients with chest CT showing exudation or consolidation in bilateral peripheral and posterior parts of the lungs were included. Early position intervention (prone or lateral) was commenced for &amp;gt; 4 hours daily for 10 days in these patients, while others received standard care. Results The baseline parameters were comparable between the position intervention group (n = 17) and the standard care group (n = 35). Position intervention was well-tolerated and increased cumulative adjusted mean difference of SpO2/FiO2 (409, 95% CI 86 to 733) and ROX index (26, 95% CI 9 to 43) with decreased Borg scale (−9, 95% CI −15 to −3) during the first 7 days. It also facilitated absorption of lung lesions and reduced the proportion of patients with high National Early Warning Score 2 (≥ 7) on days 7 and 14, with a trend toward faster clinical improvement. Virus shedding and length of hospital stay were comparable between the two groups. Conclusions This study provides the first evidence for improved oxygenation and lung lesion absorption using early position intervention in non-invasively ventilated patients with severe COVID-19, and warrants further randomized trials. </jats:sec

A Statistical Model for Estimating Maternal-Zygotic Interactions and Parent-of-Origin Effects of QTLs for Seed Development

Proper development of a seed requires coordinated exchanges of signals among the three components that develop side by side in the seed. One of these is the maternal integument that encloses the other two zygotic components, i.e., the diploid embryo and its nurturing annex, the triploid endosperm. Although the formation of the embryo and endosperm contains the contributions of both maternal and paternal parents, maternally and paternally derived alleles may be expressed differently, leading to a so-called parent-of-origin or imprinting effect. Currently, the nature of how genes from the maternal and zygotic genomes interact to affect seed development remains largely unknown. Here, we present a novel statistical model for estimating the main and interaction effects of quantitative trait loci (QTLs) that are derived from different genomes and further testing the imprinting effects of these QTLs on seed development. The experimental design used is based on reciprocal backcrosses toward both parents, so that the inheritance of parent-specific alleles could be traced. The computing model and algorithm were implemented with the maximum likelihood approach. The new strategy presented was applied to study the mode of inheritance for QTLs that control endoreduplication traits in maize endosperm. Monte Carlo simulation studies were performed to investigate the statistical properties of the new model with the data simulated under different imprinting degrees. The false positive rate of imprinting QTL discovery by the model was examined by analyzing the simulated data that contain no imprinting QTL. The reciprocal design and a series of analytical and testing strategies proposed provide a standard procedure for genomic mapping of QTLs involved in the genetic control of complex seed development traits in flowering plants

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

An Analysis of Cross-sectional Investment Portfolio with the Consideration of Risk and Return

Recently, investors are requiring diversified options on the security investment, while the sudden incidents, such as the trade war and the pandemic of COVID-19, make the investment market more volatile and turbulent. Thus, this article will discuss how investors can make rational investment decisions by using the Markowitz’s portfolio theory and its Mean-Variance Model in the U.S. investment market, in order to meet the requirement of diversification and to earn relatively stable profit. Therefore, the data spanning from 2016 to 2020 is used to provide investors with more reliable and comprehensive investment information. Meanwhile, a novel cross-section portfolio is given to fulfill the diversified and innovative investment needs of investors. The industries included are car industry, biopharmaceutical industry and financial service industry. Furthermore, the results reflect the actual situation to a large extent, including the weakness in the US market in December 2018 due to uncertain Fed policy and the impact of the COVID-19 in 2020. In this article, an Intra-Industry analysis based on the net asset values of the three targeted industries will be carried out first, then the Macro analysis will be conducted based on the optimal portfolio of the three industries. A conclusion of the findings is included at the end of the article

Discrete Element Study on Bending Resistance of Geogrid Reinforced Cement-Treated Sand

Cement-treated sand reinforced with geogrids (CTSGs) has higher bending resistance and toughness than cement-treated sands (CTSs). To explore the reinforcement mechanism of geogrids with different stiffness and layers on CTSGs, three-point bending tests and numerical tests based on DEM are carried out on CTS specimens and CTSG specimens considering different reinforcement conditions. The results show that the geogrids and cement-treated sands have good cooperative working performance. Compared with CTSs, CTSG specimens show better ductility, flexural strength and toughness. The increase in geogrid stiffness and geogrid layers promote the reinforcement effect. On the meso-level, different geogrid stiffness and layers affect the crack propagation speed and distributions of cracks due to the anchorage action of geogrids, resulting in different reinforcement effects. In addition, the layers and stiffness of geogrids affect the evolution of the internal force chains of CTSG specimens. Both the increase in geogrid layers and decrease in geogrid stiffness reduce the average internal force of geogrids and weaken the anisotropy of the normal contact force of the specimens. The simulation results interpret the reinforcement mechanism of a CTSG specimen from crack development and internal force evolution, which can support a mesoscopic supplement to laboratory tests

Targeting human caseinolytic protease P (ClpP) as a novel therapeutic strategy in ovarian cancer

Abstract Ovarian cancer (OC) is currently one of the most life‐threatening types of gynecological malignancy with limited treatment options and poor clinical outcomes. Human caseinolytic protease P (HsClpP) is located in the mitochondria and plays an important role in several tumors. Moreover, HsClpP is overexpressed in OC and several other tumor cells. Thus, HsClpP modulation is regarded as a potential approach for OC treatment. In this study, we identified and validated a novel boron peptide Compound 43‐8F as a potent HsClpP inhibitor. Upon 43‐8F treatment, mitochondrial damage was observed to be closely correlated with upregulated intracellular reactive oxygen species production, decreasement of membrane potential, and ATP content suppression. Meanwhile, the expression level of SDHB and the ATF4 was increased after 43‐8F treatment, suggesting that 43‐8F treatment induces mitochondrial respiratory disorders and activates the integrated stress response pathway to inhibit tumor cell growth. Further, 43‐8F exhibited a good therapeutic and safety profile in OC xenograft model in nude mice. Together, these results suggest that 43‐8F exerts an anti‐ovarian cancer effect by inhibiting HsClpP pathway