Sub-MIC vancomycin enhances the antibiotic tolerance of vancomycin-intermediate Staphylococcus aureus through downregulation of protein succinylation.

Bacteria develop tolerance after transient exposure to antibiotics, and tolerance is a significant driver of resistance. The purpose of this study is to evaluate the mechanisms underlying tolerance formation in vancomycin-intermediate Staphylococcus aureus (VISA) strains. VISA strains were cultured with sub-minimum inhibitory concentrations (sub-MICs) of vancomycin. Enhanced vancomycin tolerance was observed in VISA strains with distinct genetic lineages. Western blot revealed that the VISA protein succinylation (Ksucc) levels decreased with the increase in vancomycin exposure. Importantly, Ksucc modification, vancomycin tolerance, and cell wall synthesis were simultaneously affected after deletion of SacobB, which encodes a desuccinylase in S. aureus. Several Ksucc sites were identified in MurA, and vancomycin MIC levels of murA mutant and Ksucc-simulated (MurA(K69E) and MurA(K191E)) mutants were reduced. The vancomycin MIC levels of K65-MurA(K191E) in particular decreased to 1 mg/L, converting VISA strain K65 to a vancomycin-susceptible S. aureus strain. We further demonstrated that the enzymatic activity of MurA was dependent on Ksucc modification. Our data suggested the influence of vancomycin exposure on bacterial tolerance, and protein Ksucc modification is a novel mechanism in regulating vancomycin tolerance.

Efficacy of very early mobilization in patients with acute stroke: a systematic review and meta-analysis.

BACKGROUND: The incidence of stroke is increasing year by year, which seriously affects the quality of life of patients in the later period. At present, there is no clear evidence-based medical support for very early mobilization (VEM). Therefore, this study aims to systematically evaluate the effect of VEM intervention on patients with acute stroke in order to further understand the application value of VEM. METHODS: The Cochrane Library, PubMed, Embase, Web of Science, CNKI, and other databases were searched for randomized controlled trials (RCTs) on the VEM of patients with acute stroke. The articles were screened according to the inclusion and exclusion criteria. Data was extracted and the quality of the studies was evaluated. Revman 5.3 software was used to analyze the impact of VEM on adverse events after stroke, the disability rate, bed-related complications, length of hospital stay, and ability of daily living. RESULTS: After screening, 8 studies reported on the efficacy of VEM intervention for stroke patients. After analysis, VEM had no significant relationship with adverse events [relative risk (RR): 1.18; 95% confidence interval (95% CI): 0.94-1.47], disability rates (RR: 1.05; 95% CI: 0.95-1.15), and bed-related complications (RR: 0.84; 95% CI: 0.66-1.06). VEM was related to length of hospital stay [mean difference (MD): -1.72; 95% CI: -2.63 to -0.81] and ability of daily living (MD: 4.97; 95% CI: 0.15-9.79). DISCUSSION: VEM can shorten the hospital stay and improve the activities of daily living of patients. Additionally, it will not increase the adverse events, bed-related complications, and disability rates of acute stroke patients, suggesting that VEM is safe and effective.

Effects of Magnetic Nanoparticle Drug Delivery Systems on Thrombosis and Neuroprotection in Brain Stroke Model.

Nanomaterials refer to solid materials that are composed of ultrafine particles on the order of nanometers. Nanomaterials show broad application prospects in the fields of chemistry, metallurgy, electronics, aerospace, biology and medicine. The incidence of stroke in China ranks first in the world and the mortality rate is much higher than that in European and American countries. Drugs that are sensitive to the internal environment of the living body can be combined in the nuclear department to prevent them from reacting with the biological environment before reaching the target site, thereby reducing the efficacy or causing toxic side effects on other cells, tissues and organs. This project uses transgenic mice as experimental materials to establish an animal model of cerebral stroke. The light-embedded stroke model is used to simulate the pathological state of acute ischemic stroke. In vivo imaging and immunohistochemical techniques are used to analyze the administration of magnetic nanoparticles. Effects of the system on thrombolysis and neurological function protection in cerebral stroke models.

Effect of sitting and lying Liuzijue for lung rehabilitation in acute exacerbation of chronic obstructive pulmonary disease patients with non-invasive ventilation: Study protocol for a randomized controlled trial.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a lung disease with the highest incidence and high mortality in the world. Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) can significantly accelerate the progression of the disease. Pulmonary rehabilitation is one of the effective treatment methods in COPD patients, but few studies have focused on the effect of pulmonary rehabilitation in AECOPD patients. Liuzijue can improve the pulmonary function and relieve symptoms of COPD patients. However, due to the influence of disease and non-invasive ventilation (NIV), AECOPD patients have poor compliance with getting out of bed at the early stage. Sitting and lying Liuzijue is more suitable in AECOPD patients with NIV. Therefore, this study will evaluate the effect of sitting and lying Liuzijue for lung function, exercise endurance, and quality of life in AEOPD patients with NIV. METHODS: This study is a clinical randomized controlled trial. Sixty four AECOPD patients with NIV will be randomly divided into the experimental group and the control group. All participants will be treated with routine treatment and nursing according to their specific condition. The experimental group will be combined with sitting and lying Liuzijue on the basis of the control group. The duration of the exercise will be 3 months. The primary outcomes are the pulmonary function test and 6-minute walking test (6MWT). The secondary outcome measures include blood gas parameters, dyspnea index (the Modified Medical Research Council Dyspnea Scale [mMRC]), the body-mass, airflow obstruction, dyspnea and exercise capacity (BODE) index, anxiety, and depression (Hospital Anxiety and Depression Scale [HADS]), and quality of life (St·George Respiratory Questionnaire [SGRQ]). The measurement of outcomes will be evaluated at week 13. DISCUSSION: It's imperative to focus on pulmonary rehabilitation in AECOPD patients. The purpose of this study is to evaluate the effect of sitting and lying Liuzijue for pulmonary rehabilitation in AECOPD patients with NIV. TRIAL REGISTRATION: ChiCTR2000034530, Registered on July 8th, 2020.