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Abstract Neuroinflammation occurs early in Alzheimer’s disease (AD). The initial stage of AD is related to glial dysfunction, which contributes to impairment of Aβ clearance and disruption of synaptic connection. CEBPβ, a member of the CCAAT-enhancer-binding protein (CEBP) family, modulates the expression of inflammation-associated genes, and its expression is elevated in brains undergoing degeneration and injured brains. However, the mechanism underlying CEBPβ-mediated chronic inflammation in AD is unclear. In this study, we observed that increases in the levels of nuclear CEBPβ facilitated the interaction of CEBPβ with the NFκB p65 subunit, increasing the transcription of proinflammatory cytokines in the APP/PS1 mouse brain. Oral administration of nanocarrier-packaged carnosic acid (CA) reduced the aberrant activation of microglia and astrocytes and diminished mature IL-1β, TNFα and IL-6 production in the APP/PS1 mouse brain. CA administration reduced β-amyloid (Aβ) deposition and ameliorated cognitive impairment in APP/PS1 mice. We observed that CA blocked the interaction of CEBPβ with NFκB p65, and chromatin immunoprecipitation revealed that CA reduced the transcription of the NFκB target genes TNFα and IL-6. We confirmed that CA alleviated inflammatory mediator-induced neuronal degeneration and reduced Aβ secretion by inhibiting the CEBPβ-NFκB signalling pathway in vitro. Sulfobutyl ether-beta-cyclodextrin (SBEβCD) was used as the encapsulation agent for the CA-loaded nanocarrier to overcome the poor water solubility and enhance the brain bioavailability of CA. The CA nanoparticles (NPs) had no obvious toxicity. We demonstrated a feasible SBEβCD-based nanodelivery system targeting the brain. Our data provide experimental evidence that CA-loaded NPs are potential therapeutic agents for AD treatment.

Background: Oxidative stress is an early event in the development of Alzheimer's disease (AD) and maybe a pivotal point of interaction governing AD pathogenesis; oxidative stress contributes to metabolism imbalance, protein misfolding, neuroinflammation and apoptosis. Excess reactive oxygen species (ROS) are a major contributor to oxidative stress. As vital sources of ROS, mitochondria are also the primary targets of ROS attack. Seeking effective avenues to reduce oxidative stress has attracted increasing attention for AD intervention. Methods: We developed liposome‐packaged Ligustilide (LIG) and investigated its effects on mitochondrial function and AD‐like pathology in the APPswe/PS1dE9 (APP/PS1) mouse model of AD, and analyzed possible mechanisms. Results: We observed that LIG‐loaded liposome (LIG‐LPs) treatment reduced oxidative stress and β‐amyloid (Aβ) deposition and mitigated cognitive impairment in APP/PS1 mice. LIG management alleviated the destruction of the inner structure in the hippocampal mitochondria and ameliorated the imbalance between mitochondrial fission and fusion in the APP/PS1 mouse brain. We showed that the decline in cAMP‐dependent protein kinase A (PKA) and A‐kinase anchor protein 1 for PKA (AKAP1) was associated with oxidative stress and AD‐like pathology. We confirmed that LIG‐mediated antioxidant properties and neuroprotection were involved in upregulating the PKA/AKAP1 signaling in APPswe cells in vitro. Conclusion: Liposome packaging for LIG is relatively biosafe and can overcome the instability of LIG. LIG alleviates mitochondrial dysfunctions and cognitive impairment via the PKA/AKAP1 signaling pathway. Our results provide experimental evidence that LIG‐LPs may be a promising agent for AD therapy. [ABSTRACT FROM AUTHOR]

This study aims to explore the key factors influencing the processing of braised Rehmanniae Radix, optimize the processing, and determine the correlation between the components in different processed products and chroma values, which is expected to add quantitative indexes for the processing of braised Rehmanniae Radix and better control the processing. The weights of the indexes catalpol, rehmannioside D, verbascoside, isoacteoside, 5-hydroxymethylfurfural, reducing sugar, and appearance were calculated based on analytic hierarchy process(AHP) in combination with coefficient of variation, and the overall desirability(OD) was obtained. Box-Behnken design was used to explore the optimal amount of water added, time for soaking with rice wine, and steaming time in the processing of braised Rehmanniae Radix. Colorimeter was employed to determine the chroma of 17 samples and raw samples, and SPSS, Prism, and other software to investigate the correlation between the components in braised Rehmanniae Radix and the chroma values. The results showed that each factor influenced the processing, and the influence followed the order of steaming time>amount of water added>time for soaking with rice wine. The optimal processing process is as below: A total of 100 g medicinal material was added with 7 times of water, followed by soaking with rice wine for 5 h and steaming in a pot for 6 h. The correlation analysis suggested the extremely significantly positive correlation between L~* and content of catalpol, between a~* and 5-hydroxymethylfurfural content, and between b~* and catalpol content, and the extremely significantly negative correlation between L~* and the content of 5-hydroxymethylfurfural and reducing sugar, and between b~* and the content of 5-hydroxymethylfural and reducing sugar. In this experiment, response surface methodology was used to optimize the processing technology of braised Rehmanniae Radix and the optimized process was rational and feasible. The content of chemical components in braised Rehmanniae Radix was significantly correlated with the chroma. This study provided a new method for the quality evaluation of braised Rehmanniae Radix.

Objective: To discuss the characteristics of physician trainee outcomes after completion of the job-transfer subspecialty training in pediatrics, a program designed to increase the number of pediatricians, in Sichuan Province and to provide countermeasures for alleviating the shortage of pediatricians., Methods: We collected with questionnaire surveys information on changes in the workload and salaries experienced by physicians who completed the job-transfer subspecialty training program in pediatrics between February 2017 and May 2020 in Sichuan Province. Then, we compared the characteristics of physicians who successful became pediatricians and those who did no., Results: A total of 208 physicians completed the job-transfer subspecialty training program in pediatrics. Among them, 178, accounting for 85.6%, completed the questionnaire survey, and 120, accounting for 67.4%, had a background in other subspecialties than pediatrics. The majority (>90%) of physicians who participated in the training program came from secondary or lower levels of hospitals from the cities and prefectures all over Sichuan Province. In this study, we found that the rate of successful job transfer from being a physician to being a pediatrician in Sichuan Province in the past four years was 85.0% (102/120), with the year-by-year results being 88.2% (15/17) in 2017, 72.7% (16/22) in 2018, 86.7% (39/45) in 2019, and 94.% (32/34) in 2020. There was no significant difference between physicians who had successful job transfer and became pediatricians and those who failed to do so in terms of gender, age, hospital level, specialization prior to the job transfer, whether or not the hospital had a pediatrics department, amount of support for the pediatrics department, whether or not the physician was working at a new hospital after the job transfer, salaries, and changes of responsibilities during COVID-19 (all P >0.05). There was significant difference in the change of workload after completion of the training program between physicians who had successful job transfer and became pediatricians and those who failed to do so ( χ 2 =9.037, P =0.003), and 78.4% of the trainees stated that their workload had increased after the job transfer. There was a moderate correlation between successful job transfer and changes in workload after the transfer (|Phi[ψ] |=0.729)., Conclusions: The policy of government-supported job-transfer subspecialty training in pediatrics has played an active and important role in the swift resolution of the shortage of pediatricians. However, finding the root cause of and addressing the problem of the overwhelming workload of pediatricians remain challenging issues to be resolved., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)