This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

Objective To compare the detection rates and antimicrobial resistance rates of Klebsiella pneumoniae(KP)between the intensive care unit of The First People's Hospital of Changzhou(CZFPH-ICU)and the American Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ),as well as the changes in the antimicrobial resistance rate of KP and detection rate of carbapenem-resistant KP(CRKP)in CZFPH-ICU.Methods Differences in speci-men distribution and antimicrobial resistance rate of KP detected from CZFPH-ICU and MIMIC-Ⅳ from 2017 to 2019,as well as the changing trends of specimen distribution,antimicrobial resistance rate,detection rates of KP and CRKP from different specimen sources in CZFPH-ICU from 2017 to 2023 were retrospectively analyzed.Results A total of 2 434 strains of KP were detected in CZFPH-ICU from 2017 to 2019,mainly from sputum specimens.A total of 1 137 strains of KP were detected from MIMIC-Ⅳ database,mainly from urine specimens.Compared with MIMIC-Ⅳ,KP detected from CZFPH-ICU showed higher resistance rate to commonly used antimicrobial agents.A total of 4 874 strains of KP were detected from CZFPH-ICU from 2020 to 2023,mainly from sputum specimens.The detection rates of CRKP from sputum,urine,drainage fluid and bile specimens decreased from 17.77％,20.15％,24.22％and 24.07％in 2017-2019 to 12.99％,13.56％,13.63％and 8.00％in 2020-2023,respectively(all P＜0.05).The changing trend of resistance rate of KP isolated from CZFPH-ICU from 2017 to 2023 to commonly used antimicrobial agents such as piperacillin/tazobactam,imipenem,and meropenem increased in 2017-2019,decreased in 2020-2022,and slightly increased in 2023.In 2013,the resistance rates of KP isolated from CZFPH-ICU to ceftazidime/avibactam,polycolistin B and tigacycline were 21.28％,10.22％and 7.03％,respectively.Conclusion In recent 7 years,resistance rate of KP from CZFPH-ICU showed a slow decline trend,but it was still higher than that in foreign MIMIC-Ⅳ database.Hospitals should strengthen various infection prevention and control measures to ef-fectively control KP resistance and infection.

Since 2005, GLP-1 receptor (GLP-1R) agonists (GLP-1RAs) have been developed as therapeutic agents for type 2 diabetes (T2D). GLP-1R is not only expressed in pancreatic islets but also other organs, especially the lung. However, controversy on extra-pancreatic GLP-1R expression still needs to be further resolved, utilizing different tools including the use of more reliable GLP-1R antibodies in immune-staining and co-immune-staining. Extra-pancreatic expression of GLP-1R has triggered extensive investigations on extra-pancreatic functions of GLP-1RAs, aiming to repurpose them into therapeutic agents for other disorders. Extensive studies have demonstrated promising anti-inflammatory features of GLP-1RAs. Whether those features are directly mediated by GLP-1R expressed in immune cells also remains controversial. Following a brief review on GLP-1 as an incretin hormone and the development of GLP-1RAs as therapeutic agents for T2D, we have summarized our current understanding of the anti-inflammatory features of GLP-1RAs and commented on the controversy on extra-pancreatic GLP-1R expression. The main part of this review is a literature discussion on GLP-1RA utilization in animal models with chronic airway diseases and acute lung injuries, including studies on the combined use of mesenchymal stem cell (MSC) based therapy. This is followed by a brief summary.