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PURPOSE: Previous studies showed that long-term use of proton pump inhibitors (PPIs) was associated with cardiovascular events. However, the impact of short-term PPI exposure on intensive care unit (ICU) patients with myocardial infarction (MI) remains largely unknown. This study aims to determine the precise correlation between short-term PPI usage during hospitalization and prognostic outcomes of ICU-admitted MI patients using Medical Information Mart for Intensive Care IV database (MIMIC-IV). METHODS: Propensity score matching (PSM) was applied to adjust confounding factors. The primary study outcome was rehospitalization with mortality and length of stay as secondary outcomes. Binary logistic, multivariable Cox, and linear regression analyses were employed to estimate the impact of short-term PPI exposure on ICU-admitted MI patients. RESULTS: A total of 7249 patients were included, involving 3628 PPI users and 3621 non-PPI users. After PSM, 2687 pairs of patients were matched. The results demonstrated a significant association between PPI exposure and increased risk of rehospitalization for MI in both univariate and multivariate [odds ratio (OR) = 1.157, 95% confidence interval (CI) 1.020-1.313] analyses through logistic regression after PSM. Furthermore, this risk was also observed in patients using PPIs > 7 days, despite decreased risk of all-cause mortality among these patients. It was also found that pantoprazole increased the risk of rehospitalization, whereas omeprazole did not. CONCLUSION: Short-term PPI usage during hospitalization was still associated with higher risk of rehospitalization for MI in ICU-admitted MI patients. Furthermore, omeprazole might be superior to pantoprazole regarding the risk of rehospitalization in ICU-admitted MI patients.
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It is urgent to develop new antiviral agents due to the continuous emergence of drug-resistant strains of influenza virus. Our earlier studies have identified that certain pentacyclic triterpene saponins with 3-O-ß-chacotriosyl residue are novel H5N1 virus entry inhibitors. In the present study, a series of C-28 modified 3-O-ß-chacotriosyl epiursolic acid derivatives via conjugation with different kinds of sides were synthesized, of which anti-H5N1 activities in A549 cells were evaluated in vitro. Among them, 10 exhibited strongest anti-H5N1 potency at the low-micromole level without cytotoxicity, surpassing the potency of ribavirin. Further mechanism studies of the lead compound 10 based on HI, SPR and molecular modeling revealed that these new 3-epiursolic acid saponins could bind tightly to the viral envelope HA protein, thus blocking the invasion of H5N1 viruses into host cells.
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Antivirales/farmacología , Subtipo H5N1 del Virus de la Influenza A/efectos de los fármacos , Triterpenos/farmacología , Internalización del Virus/efectos de los fármacos , Células A549 , Antivirales/síntesis química , Antivirales/química , Relación Dosis-Respuesta a Droga , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Relación Estructura-Actividad , Triterpenos/síntesis química , Triterpenos/química , Ácido UrsólicoRESUMEN
In order to develop energy storage devices with high power performance, electrodes should hold well-defined pathways for efficient ionic and electronic transport. Herein, we demonstrate a highly conductive graphene nanosheet/nanometer-sized carbide-derived carbon framework (hcGNS/nCDC). In this architecture, nCDC possesses short transport paths for electrolyte ions, thus ensuring the rapid ions transportation. The excellent electrical conductivity of hcGNS can reduce the electrode internal resistance for the supercapacitor and thus endows the hcGNS/nCDC composite electrodes with excellent electronic transportation performance. Electrochemical measurements show that the cyclic voltammogram of hcGNS/nCDC can maintain a rectangular-like shape with the increase of the scan rate from 5 mV s-1 to 20 V s-1, and the specific capacitance retention is up to 51% even at a high scan rate of 20 V s-1, suggesting ultrahigh power performance, which, to the best of our knowledge, is among the best power performances reported so far for the carbon materials. Furthermore, the hcGNS/nCDC composite also shows an excellent cycling stability (no drop in its capacitance occurs even after 10000 cycles). This work demonstrates the advantage in the ultrahigh power performance for the framework having both short transport pathways for electrolyte ions and high electrical conductivity.
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We propose a novel and facile synthesis approach to a porous carbon/graphene composite. Graphene is obtained from room-temperature expanded graphite (RTEG), not involving the use of graphite oxide (GO). Porous carbon is acquired by carbonization and KOH-activation of polyvinylpyrrolidone (PVP), which is used to exfoliate RTEG into graphene and inhibit the restacking of the resultant graphene in the present work. The prepared porous carbon/graphene composite has a high specific surface area (SSA) (3008 m2 g-1) and a hierarchical micro- and meso- pore structure (dominant pores in the range of 1-5 nm). Electrochemical measurement demonstrates that the as-prepared porous carbon/graphene composite can deliver an outstanding specific capacitance of up to 340 F g-1 at 5 mV s-1 in 6 M KOH electrolyte. This specific capacitance is among the highest reported so far for porous carbon/graphene materials. Moreover, the prepared composite as an electrode material also exhibits excellent cycling stability (94.4% capacitance retention over 10 000 cycles). The as-fabricated symmetrical supercapacitor exhibits a high energy density of 10.9 W h kg-1 (based on total mass of electrode materials) and an outstanding energy density retention, even at high power density. Compared with conventional preparation routes for porous carbon/graphene composites, the present approach is significantly simple, convenient and cost-effective, which will make it more competent in the development of electrode materials for high-performance supercapacitors.
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Previous studies found that histamine H2 receptor antagonists (H2RAs) had blood pressure lowering and cardioprotective effects, but the impact of H2RAs on the survival outcomes of critically ill patients with essential hypertension is still unclear. The aim of this study was to investigate the association of H2RAs exposure with all-cause mortality in patients with essential hypertension based on Medical Information Mart for Intensive Care III database. A total of 17,739 patients were included, involving 8482 H2RAs users and 9257 non-H2RAs users. Propensity score matching (PSM) was performed to improve balance between 2 groups that were exposed to H2RAs or not. Kaplan-Meier survival curves were used to compare the cumulative survival rates and multivariable Cox regression models were performed to evaluate the association between H2RAs exposure and all-cause mortality. After 1:1 PSM, 4416 pairs of patients were enrolled. The results revealed potentially significant association between H2RAs exposure and decreased 30-day, 90-day, and 1-year mortalities in multivariate analyses (HR = 0.783, 95% CI: 0.696-0.882 for 30-day; HR = 0.860, 95% CI: 0.778-0.950 for 90-day; and HR = 0.883, 95% CI: 0.811-0.961 for 1-year mortality, respectively). Covariate effect analyses showed that the use of H2RAs was more beneficial in essential hypertension patients with age ≥ 60, BMI ≥ 25 kg/m2, coronary arteriosclerosis, stroke, and acute kidney failure, respectively. In conclusion, H2RAs exposure was related to lower mortalities in critically ill patients with essential hypertension, which provided novel potential strategy for the use of H2RAs in essential hypertension patients.
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Enfermedad Crítica , Hipertensión Esencial , Antagonistas de los Receptores H2 de la Histamina , Humanos , Masculino , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Hipertensión Esencial/tratamiento farmacológico , Hipertensión Esencial/mortalidad , Anciano , Enfermedad Crítica/mortalidadRESUMEN
Background: Our previous study reported that histamine H2 receptor antagonists (H2RAs) exposure was associated with decreased mortality in critically ill patients with heart failure (HF) through the same pharmacological mechanism as ß-blockers. However, population-based clinical study directly comparing the efficacy of H2RAs and ß-blockers on mortality of HF patients are still lacking. This study aims to compare the association difference of H2RAs and ß-blockers on mortality in critically ill patients with HF using the Medical Information Mart for Intensive Care III database (MIMIC-III). Methods: Study population was divided into 4 groups: ß-blockers + H2RAs group, ß-blockers group, H2RAs group, and Non-ß-blockers + Non-H2RAs group. Kaplan-Meier curves and multivariable Cox regression models were employed to evaluate the differences of all-cause mortalities among the 4 groups. Propensity score matching (PSM) was used to increase comparability of four groups. Results: A total of 5593 patients were included. After PSM, multivariate analyses showed that patients in H2RAs group had close all-cause mortality with patients in ß-blockers group. Furthermore, 30-day, 1-year, 5-year and 10-year all-mortality of patients in ß-blockers + H2RAs group were significantly lower than those of patients in ß-blockers group, respectively (HR: 0.64, 95%CI: 0.50-0.82 for 30-day; HR: 0.80, 95%CI: 0.69-0.93 for 1-year mortality; HR: 0.83, 95%CI: 0.74-0.93 for 5-year mortality; and HR: 0.85, 95%CI: 0.76-0.94 for 10-year mortality, respectively). Conclusion: H2RAs exposure exhibited comparable all-cause mortality-decreasing effect as ß-blockers; and, furthermore, H2RAs and ß-blockers had additive or synergistic interactions to improve survival in critically ill patients with HF.
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Currently, SARS-CoV-2 virus is an emerging pathogen that has posed a serious threat to public health worldwide. However, no agents have been approved to treat SARS-CoV-2 infections to date, underscoring the great need for effective and practical therapies for SARS-CoV-2 outbreaks. We reported that a focused screen of OA saponins identified 3-O-ß-chacotriosyl OA benzyl ester 2 as a novel small molecule inhibitor of SARS-CoV-2 virus entry, via binding to SARS-CoV-2 glycoprotein (S). We performed structure-activity relationship profiling of 2 and discovered C-17-COOH of OA was an important modification site that improved both inhibitor potency toward SARS-CoV-2 and selectivity index. Then optimization from hit to lead resulted in a potent fusion inhibitor 12f displaying strong inhibition against infectious SARS-CoV-2 with an IC50 value of 0.97 µM in vitro. Mechanism studies confirmed that inhibition of SARS-CoV-2 viral entry of 12f was mediated by the direct interaction with SARS-CoV-2 S2 subunit to block membrane fusion. These 3-O-ß-chacotriosyl OA amide saponins are suitable for further optimization as SARS-CoV-2 entry inhibitors with the potential to be developed as therapeutic agents for the treatment of SARS-CoV-2 virus infections.