Exploring the mechanisms of glycolytic genes involvement in pulmonary arterial hypertension through integrative bioinformatics analysis.

The purpose of this study was to identify the mechanisms underlying the involvement of glycolytic genes in pulmonary arterial hypertension (PAH). This study involved downloading 3 datasets from the GEO database at the National Center for Biotechnology Information. The datasets were processed to obtain expression matrices for analysis. Genes involved in glycolysis-related pathways were obtained, and genes related to glycolysis were selected based on significant differences in expression. Gene Ontology functional annotation analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and GSEA enrichment analysis were performed on the DEGs. Combining LASSO regression with SVM-RFE machine learning technology, a PAH risk prediction model based on glycolysis related gene expression was constructed, and CIBERSORTx technology was used to analyse the immune cell composition of PAH patients. Gene enrichment analysis revealed that the DEGs work synergistically across multiple biological pathways. A total of 6 key glycolysis-related genes were selected using LASSO regression and SVM. A bar plot was constructed to evaluate the weights of the key genes and predict the risk of PAH. The clinical application value and predictive accuracy of the model were assessed. Immunological feature analysis revealed significant correlations between key glycolysis-related genes and the abundances of different immune cell types. The glycolysis genes (ACSS2, ALAS2, ALDH3A1, ADOC3, NT5E, and TALDO1) identified in this study play important roles in the development of pulmonary arterial hypertension, providing new evidence for the involvement of glycolysis in PAH.

Construction and validation of a nomogram for predicting remission of migraine patients with patent foramen ovale after closure.

OBJECTIVE: This study aimed to construct and validate a nomogram model that predicts the remission of migraine attacks by screening factors that affect the prognosis of migraine patients with patent foramen ovale (PFO) after closure. METHOD: Retrospective analysis was conducted in migraine patients with PFO who underwent PFO closure in the Department of Cardiology of Jiangsu Province Hospital from September 2020 to April 2023. Based on the Migraine Disability Assessment (MIDAS) scores from the 1-year follow-up after PFO closure, all patients who met the inclusion criteria were categorized into a remission group and a non-remission group. The primary efficacy endpoint was remission of migraine headache. After collecting clinical data, transcranial doppler sonography (TCD) results and MIDAS scores, LASSO (least absolute shrinkage and selection operator) regression and multivariable logistic regression analysis were used to filter variables predictive to migraine remission and construct the nomogram model. The Nomogram's accuracy and consistency were respectively assessed through Receiver Operating Characteristic (ROC) curves and calibration curves. Additionally, an analysis of decision curves (DCA) was conducted to evaluate the clinical utility of this newly developed model. RESULT: A total of 241 consecutive patients were included in the study. The remission group included 21 males and 93 females, with a median age of 39 (30.25,50) years. The non-remission group included 26 males and 101 females, with a median age of 35 (25.5,47.5) years. All Patients were randomly divided into a training cohort and a validation cohort. Multivariable logistic regression analysis showed that 5 independent predictors, including MIDAS before closure (p = 0.0002), mitigating factors (p = 0.0057), number of attacks/month (p = 0.0058), TCD (p = 0.0093) and Platelet Crit (PCT) (p = 0.0351), played a significant role in the prediction of remission of migraine patients with PFO after closure. Based on these independent predictors, the predictive nomogram model of migraine remission in PFO patients was constructed. The application of the nomogram in the training cohort exhibited good discrimination (area under the ROC curve was 0.7763[95% CI 0.7108-0.8418]), which was confirmed in the validation cohort (AUC was 0.704[95% CI 0.5533-0.8547]). The calibration curve showed that the nomogram model demonstrated good calibration performance. Additionally, the decision curve analysis indicated the clinical utility of the nomogram model. CONCLUSION: The construction of the nomogram model had a considerable predictive accuracy for migraine remission in patients after PFO closure, which may provide constructive guidance for clinical decision making.

Comparison of the short-term efficacy of different Amplatzer models and similar occluders in the treatment of patent foramen ovale.

Objective: To compare the recent efficacy and safety of different Amplatzer models and similar occluder in the treatment of patent foramen ovale (PFO). Methods: Patients with PFO complicated with cryptogenic stroke or migraine who underwent transcatheter closure of PFO in the First Affiliated Hospital of Nanjing Medical University from September 2019 to March 2021 were selected. Patients were grouped according to the type of occluder device. The basic data of the patients were collected and followed up within 1 year after occlusion. Effectiveness was defined as no recurrence of stroke/remission of migraine symptoms and a negative postoperative foaming test, and safety events were counted as the combined results of serious adverse events. Results: A total of 92 patients were selected, including 45 cases in the symmetrical group and 47 cases in the asymmetric group. There were no serious adverse events in the 2 groups during follow-up. 3 days and 1 month after occlusion, the number of shunt patients in the asymmetric group was significantly less than that in the symmetric group (χ2 = 5.484, P = 0.019; χ2 = 5.146, P = 0.023). The negative rate of blocked residual shunts in the asymmetric group was higher than that in the symmetric group at 1, 3, 6 and 12 months after occlusion (χ2 = 6.473, P = 0.011; χ2 = 4.305, P = 0.038; χ2 = 4.842, P = 0.027; χ2 = 4.034, P = 0.045). Headache in migraine patients in the asymmetric group was significantly better than headache in patients in the symmetric group (P = 0.038; P = 0.049). Conclusion: Asymmetric Amplatzer and similar occluders provide greater efficacy in short-term occlusion than symmetric ones.

Monocyte-to-lymphocyte ratio predicts mortality and cardiovascular mortality in the general population.

BACKGROUND: Systemic chronic inflammation (SCI) is closely involved in the pathogenesis of many diseases. This study aims to investigate the association between MLR with mortality and cardiovascular disease (CVD) mortality in US adults. METHODS: 35,813 adults were enrolled from the 1999-2014 National Health and Nutrition Examination Survey (NHANES) cycle. Individuals were categorized according to MLR tertiles and followed until 31 December 2019. Kaplan-Meier plots and log-rank tests were utilized to explore survival differences among the MLR tertiles. Adjusted multivariable Cox analysis was employed to investigate the relationship of MLR with mortality and CVD mortality. Restricted cubic spline and subgroup analysis were further used to discern non-linear relationship and the relationship in categories. RESULTS: During a median follow-up of 134 months, 5865 (16.4%) all-cause deaths and 1602 (4.5%) cardiovascular deaths occurred. Kaplan-Meier plots revealed significant differences in all-cause and cardiovascular mortality among the MLR tertiles. In the fully-adjusted Cox regression model, individuals in the highest tertile of MLR had higher risk of mortality (HR = 1.26, 95% CI: 1.17-1.35) and CVD mortality (HR = 1.41, HR, 95% CI: 1.23-1.62) than those in the lowest tertile. The restricted cubic spline exhibited a J-shaped relationship between MLR with mortality and CVD mortality (P for non-linearity <0.001). The further subgroup analysis demonstrated a robust trend across categories. CONCLUSION: Our study demonstrated that increased baseline MLR was positively associated with a higher risk of death in US adults. MLR was a strong independent predictor of mortality and CVD mortality in the general population.

Coronatine-Based Gene Expression Changes Impart Partial Resistance to Fall Armyworm (Spodoptera frugiperda) in Seedling Maize.

In recent years, Spodoptera frugiperda (S. frugiperda, Smith) has invaded China, seriously threatening maize production. To explore an effective method to curb the further expansion of the harm of the S. frugiperda, this experiment used maize seedlings of the Zhengdan 958 three-leaf stage (V3) of maize as the material to study the effect of coronatine (COR) on the ability of maize to resist insects (S. frugiperda) at the seedling stage. The results showed that when maize was sprayed with 0.05 µM COR, the newly incubated larvae of S. frugiperda had the least leaf feeding. It was found that 0.05 µM COR significantly increased the contents of abscisic acid (ABA) and jasmonate (JA) in maize leaves through the determination of hormone content. Moreover, transcriptome sequencing revealed that the expression of six genes (ZmBX1, ZmBX2, ZmBX3, ZmBX4, ZmBX5 and ZmBX6), which are associated with the synthesis of benzoxazinoid, were upregulated. Nine genes (ZmZIM3, ZmZIM4, ZmZIM10, ZmZIM13, ZmZIM18, ZmZIM23, ZmZIM27, ZmZIM28 and ZmZIM38) of JA-Zim Domain (JAZ) protein in the JA signal pathway, and seven genes (ZmPRH19, ZmPRH18, Zm00001d024732, Zm00001d034109, Zm00001d026269, Zm00001d028574 and Zm00001d013220) of ABA downstream response protein Group A Type 2C Protein Phosphatase (PP2C) were downregulated. These results demonstrated that COR could induce anti-insect factors and significantly improve insect resistance in seedling maize, which laid a theoretical foundation for further study of the mechanism of COR improving insect resistance in seedling maize, and provided data references for the use of COR as an environmentally friendly pest control method.

Neuroprotective Mechanisms of Ginsenoside Rb1 in Central Nervous System Diseases.

Panax ginseng and Panax notoginseng, two well-known herbs with enormous medical value in Asian countries, have a long usage history in China for the therapy of some diseases, such as stroke. Ginsenoside Rb1 is one of most important active ingredients in Panax ginseng and Panax notoginseng. In the last two decades, more attention has focused on ginsenoside Rb1 as an antioxidative, anti-apoptotic and anti-inflammatory agent that can protect the nervous system. In the review, we summarize the neuroprotective roles of ginsenoside Rb1 and its potential mechanisms in central nervous system diseases (CNSDs), including neurodegenerative diseases, cerebral ischemia injury, depression and spinal cord injury. In conclusion, ginsenoside Rb1 has a potential neuroprotection due to its inhibition of oxidative stress, apoptosis, neuroinflammation and autophagy in CNSDs and may be a promising candidate agent for clinical therapy of CNSDs in the future.

Clinical outcomes of bariatric surgery - Updated evidence.

Obesity has grown to become a major health problem over the past few decades. Obesity-related comorbidities, such as diabetes mellitus, hypertension, obstructive sleep apnea, and dyslipidemia, are inextricably linked with increased adverse clinical consequences and mortality. Compared with other strategies for obesity, bariatric surgery is efficient in weight loss and has been proved to exert positive effects on obesity-related risk factors. This broad improvement in risk factors has resulted in substantial remission or reductions of comorbidities and better performance on clinical outcomes, including cardiovascular diseases, cancer, and mortality. With the development of surgical procedures, the safety of bariatric surgery has been validated and the rate of peri-operative death is low all over the world. Nonetheless, surgeons ought to be careful about potential complications, such as nutrition deficiencies, psychological disorders, or new digestive tract tumors after surgery. For patients with obesity, bariatric surgery might be a precious and crucial tool to bring additional benefits including comorbidities protection and life span extension. All patients with obesity should be engaged in a union consultation group to select a suitable treatment.

Cardiotoxicity in cancer immune-checkpoint therapy: Mechanisms, clinical evidence, and management strategies.

Immune-checkpoint inhibitors (ICIs), a unique antibody-based therapeutic strategy, have revolutionized the treatment landscape of solid and hematological cancers. Despite the proven benefits of ICIs, the cardiotoxicity from unspecific immune activation (uncommon but potentially fatal) is a continuing concern. Accumulating preclinical research has demonstrated that ICIs initiate inflammation in the myocardium, while clinically significant cardiotoxicity were reported in few patients receiving ICI therapy, probably due to the low incidence and unspecific symptoms. The subtle signs and symptoms (e.g., chest pain, dizziness, and dyspnea) were likely attributed to cancer and/or non-cardiac events by previous studies, thus limiting the understanding of the incidence, outcomes, risk factors, and management of ICI-related cardiotoxicity. The heterogeneous clinical presentation and complex diagnostic procedure further make it challenging to accurately identify ICI-related cardiac events in clinical trials. Therefore, ICI-related cardiotoxicity, whose incidence is probably underestimated, has not been well recognized. In this article, we provide an overview of potential mechanisms underlying ICI-related cardiotoxicity and review accumulating clinical evidence of ICI-related cardiotoxicity, with a focus on myocarditis. Moreover, we discuss possible strategies to manage ICI-related cardiotoxicity and highlight the importance of developing cardio-oncology.