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Background: The physiologic and anthropometric characteristics changes associated with obesity may result in the alternation of pharmacologic management. Remimazolam tosylate is a new type of ultra-short-acting benzodiazepine with stable context-sensitive half-time (CSHT) and no lipid accumulation after long-time infusion. Although remimazolam tosylate has potential advantages for the induction and maintenance of anesthesia in obese patients, the appropriate induction dosing scalars among obese patients are unknown. Therefore, we aim to compare the different weight-based scalars for dosing remimazolam tosylate of anesthesia induction among obese patients. Methods/design: The study will be performed as a prospective, single-center, double-blind, controlled clinical trial. The study design is a comparison of remimazolam tosylate requirements based on total body weight (TBW) or lean body weight (LBW) to reach a Modified Observer's Assessment of Alertness and Sedation (MOAA/S) score of 0 among obese subjects (BMI ≥ 35 kg/m2). Another twenty normal-weight subjects (18.5 kg/m2 ≤ BMI < 25 kg/m2) will be enrolled as a control group, whose induction dose is scaled based on TBW. The infusion rate of remimazolam tosylate during induction is 12 mg/kg/h in all groups. Discussion: Results of the present study will provide evidence of dose scalar of remimazolam tosylate to guide the clinical practice of anesthesia induction in obese patients. Trial registration: Chinese Clinical Trial Registry ChiCTR220005664. Registered on 9 February 2022, https://www.chictr.org.cn/showproj.aspx?proj=151150. [ABSTRACT FROM AUTHOR]

Background: No nomogram has been established to predict the incidence of major postoperative respiratory adverse events (mPRAEs) in children undergoing rigid bronchoscopy for airway foreign bodies (AFB) removal and exploration of the airway, though some studies have confirmed the risk factors. Methods: 1214 pediatric patients (≤3 years old) undergoing rigid bronchoscopy for AFB from June 2014 to December 2020 were enrolled in this study. The primary outcome was the occurrence of mPRAEs, including laryngospasm and bronchospasm. Following that, a nomogram prediction model for the mPRAEs was developed. Results: The incidence of mPRAEs was 84 (6.9%) among 1214 subjects. American Society of Anesthesiologists physical status (ASA-PS), intraoperative desaturation (SpO2 < 90%), procedural duration and ventilatory approach were all independent risk factors of mPRAEs. The area under the receiver operating characteristic curve (AUC) value of the nomogram for predicting mPRAEs was 0.815 (95% CI: 0.770–0.861), and the average AUC for ten-fold cross-validation was 0.799. These nomograms were well calibrated by Hosmer-Lemshow (p = 0.607). Decision curve analysis showed that the nomogram prediction model is effective in clinical settings. Conclusions: Combining ASA-PS, intraoperative desaturation, procedural duration, and ventilatory approach, the nomogram model is adequate for predicting the risk of developing mPRAEs, followed by rigid bronchoscopy for AFB removal and exploration. [ABSTRACT FROM AUTHOR]

Stem-cell-based therapy is very promising for Alzheimer's disease (AD), yet has not become a reality. A critical challenge is the transplantation microenvironment, which impacts the therapeutic effect of stem cells. In AD brains, amyloid-beta (Aβ) peptides and inflammatory cytokines continuously poison the tissue microenvironment, leading to low survival of grafted cells and restricted efficacy. It is necessary to create a growth-supporting microenvironment for transplanted cells. Recent advances in AD studies suggest that the asparaginyl endopeptidase (AEP) is a potential intervention target for modifying pathological changes. We here chose APP/PS1 mice as an AD model and employed pharmacological inhibition of the AEP for one month to improve the brain microenvironment. Thereafter, we transplanted neural stem cells (NSCs) into the hippocampus and maintained therapy for one more month. We found that inhibition of AEPs resulted in a significant decrease of Aβ, TNF-α, IL-6 and IL-1β in their brains. In AD mice receiving NSC transplantation alone, the survival of NSCs was at a low level, while in combination with AEP inhibition pre-treatment the survival rate of engrafted cells was doubled. Within the 2-month treatment period, implantation of NSCs plus pre-inhibition of the AEP significantly enhanced neural plasticity of the hippocampus and rescued cognitive impairment. Neither NSC transplantation alone nor AEP inhibition alone achieved significant efficacy. In conclusion, pharmacological inhibition of the AEP ameliorated brain microenvironment of AD mice, and thus improved the survival and therapeutic efficacy of transplanted stem cells. [ABSTRACT FROM AUTHOR]

Proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) are related proteins exclusive to Mycobacteria that play diverse roles in modulating critical innate immune pathways. In this study, we observed that the PPE57 protein is associated with the cell wall and is exposed on the cell surface. PPE57 enhances Mycobacterium spp. entering into macrophages and plays a role in macrophage phagocytosis. To explore the underlying mechanism, we demonstrated that PPE57 is able to recognise Toll-like receptor 2 (TLR2) and further induce macrophage activation by augmenting the expression of several cell surface molecules (CD40, CD80, CD86 and MHC class II) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-12p40) within macrophages. These molecules are involved in the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signalling pathways. We demonstrated that PPE57 effectively polarises T cells to secrete interferon (IFN)-γ and IL-2 and to up-regulate CXCR3 expression in vivo and in vitro, suggesting that this protein may contribute to Th1 polarisation during the immune response. Moreover, recombinant Bacillus Calmette-Guérin (BCG) over-expressing PPE57 could provide better protective efficacy against Mycobacterium tuberculosis challenge compared with BCG. Taken together, our data provides several pieces of evidence that PPE57 may regulate innate and adaptive immunity by interacting with TLR2. These findings indicate that PPE57 protein is a potential antigen for the rational design of an efficient vaccine against M. tuberculosis. Key messages: [ABSTRACT FROM AUTHOR]

The Cole function is widely used in bioimpedance spectroscopy (BIS) applications. Fitting the measured BIS data onto the model and then extracting the Cole parameters (R0, R∞, α and τ) is a common practice. Accurate extraction of the Cole parameters from the measured BIS data has great significance for evaluating the physiological or pathological status of biological tissue. The traditional least-squares (LS)-based curve fitting method for Cole parameter extraction is often sensitive to noise or outliers and becomes non-robust. This paper proposes an improved Cole parameter extraction based on the least absolute deviation (LAD) method. Comprehensive simulation experiments are carried out and the performances of the LAD method are compared with those of the LS method under the conditions of outliers, random noises and both disturbances. The proposed LAD method exhibits much better robustness under all circumstances, which demonstrates that the LAD method is deserving as an improved alternative to the LS method for Cole parameter extraction for its robustness to outliers and noises. [ABSTRACT FROM AUTHOR]