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Context: Antibiotic resistance is a major clinical and public health problem. Development of new therapeutic approaches to prevent bacterial multidrug resistance during antimicrobial chemotherapy has thus been becoming a primary consideration in the medicinal chemistry community. Objective: We described a new strategy that combats multidrug resistance by using natural medicines to target the druggable enzymome (i.e., enzymatic proteome) ofStaphylococcus aureus. Materials and methods: A pipeline of integratingin silicoanalysis andin vitroassay was purposed to identify antibacterial agents from a large library of natural products with diverse structures, high drug-likeness, and relatively low flexibility, with which a systematic interactome of 826 natural product candidates with 125 functionally essentialS. aureusenzymes was constructed via a high-throughput cross-docking approach. The obtained docking score matrix was then converted into an array of synthetic scores; each corresponds to a natural product candidate. By systematically examining the docking results, a number of highly promising candidates with potent antibacterial activity were suggested. Results: Three natural products, i.e., radicicol, jorumycin, and amygdalin, have been determined to possess strong broad-spectrum potency combating both the drug-resistant and drug-sensitive strains (MIC value <10 μg/ml). In addition, some natural products such as tetrandrine, bilobalide, and arbutin exhibited selective inhibition on different strains. Discussion and conclusion: Combined quantum mechanics/molecular mechanics analysis revealed diverse non-bonded interactions across the complex interfaces of newly identified antibacterial agents with their putative targets GyrB ATPase and tyrosyl-tRNA synthetase. [ABSTRACT FROM AUTHOR]

Background: The intra-aortic balloon pump (IABP) technique plays a crucial role in providing circulatory support for patients experiencing hemodynamic instability. This study aimed to assess the effectiveness and safety of preoperative prophylactic IABP insertion in patients undergoing acute critical coronary artery bypass grafting (CABG)., Methods: A comprehensive search was conducted in PubMed, Cochrane Library, and Embase databases, covering the period from January 1995 to September 2022., Results: The incidence of renal insufficiency, mechanical ventilation exceeding 24 h, and bleeding events in the IABP group did not exhibit significant differences compared to the control group (relative risk [RR] = 0.85, P = 0.26; RR = 0.81, P = 0.08; RR = 0.95, P = 0.87). However, the hospital mortality rate was significantly lower in the IABP group than in the control group (RR = 0.54, P = 0.0007), and the length of ICU stay was shorter in the IABP group (mean difference [MD] = -1.12, P < 0.000001). The IABP group also exhibited a lower incidence of low cardiac output syndrome (LCOS%) compared to the control group (RR = 0.61, P < 0.0001), and a lower incidence of major adverse cardiac and cerebrovascular events (MACCE%) (RR = 0.70, P = 0.001). No significant publication bias was observed in the funnel plot analysis., Conclusion: Preoperative prophylactic insertion of IABP is currently considered beneficial in improving outcomes for critically ill patients undergoing CABG. This technique reduces hospital mortality, shortens ICU stays, and lowers the incidence of LCOS% and MACCE%., (© 2024. The Author(s).)