ObjectiveTo develop a community-family management model for older adults with mild cognitive impairment (MCI) and to formulate detailed application specifications, and to fully leverage the initiative of communities and families under limited resource conditions, for achieving community-based early detection and early intervention for older adults with MCI. MethodsA systematic literature review was conducted to identify pertinent publications. Corpus-based research methodologies were employed to extract, refine, integrate and synthesize management elements, thereby establishing the specific content and service processes for each stage of the management model. Utilizing the 5W2H analytical framework, essential elements such as management stakeholders, target populations, content and methods for each stage were delineated. The model and its application guidelines were finalized through expert consultation and demonstration. ResultsAn expert evaluation of the management model yielded mean scores of 4.84, 4.32 and 4.84 for acceptability, feasibility and systematicity, respectively. By integrating the identified core elements with expert ratings and feedback, the final iteration of the community-family management model for older adults with MCI was formulated. This model comprised of five stages: screening and identification, comprehensive assessment, intervention planning, monitoring and referral pathways to ensure implementation, and enhanced support for communities, family members and caregivers. Additionally, it included 18 specific application guidelines. ConclusionThe proposed management model may theoretically help delay cognitive decline, improve cognitive function and potentially promote reversal from MCI to normal cognition. It may also enhance the awareness and coping capacity of older adults and their families, strengthen community healthcare professionals' ability to early identify and manage MCI.

Objective To investigate the effect of midazolam on neuronal damage in ischemic stroke （IS） rats and its regulatory effect on PTEN-induced putative kinase 1 （PINK1）/E3 ubiquitin ligase （PARKIN） signaling pathway. Methods An IS rat model was established using arterial occlusion method. The rats with successful model were randomly divided into IS group, drug-low, medium, high-dose （drug-L, M, H, 30, 60, 90 mg/kg midazolam） groups, drug-H+autophagy inhibitor 3-MA group （90 mg/kg midazolam+30 mg/kg 3-MA）, and rats with only isolated blood vessels were used as sham surgery groups. Each group received corresponding doses of drugs or physiological saline intervention, and the neurological function scoring, brain histopathology, neuronal apoptosis, ultrastructure, and expression of PINK1, PARKIN, microtubule-associated protein 1 light chain 3 （LC3）, and P62 protein in mitochondria were detected. Results Compared with the IS group, the pathological damage of the drug-L group, drug-M group, and drug-H group was improved, and autophagosomes showed an increasing trend, the expression of PINK1, PARKIN, and LC3 proteins increased, the neurological function score, neuronal apoptosis rate, and P62 protein obviously decreased in a dose-dependent manner （P<0.01 or P<0.001）; compared with the drug-H group, the pathological damage in the drug-H+3-MA group increased and autophagosomes decreased, the expression of PINK1, PARKIN, and LC3 proteins decreased, the neurological function score, neuronal apoptosis rate, and P62 protein obviously increased （P<0.001）. Conclusion Midazolam induced mitochondrial autophagy in IS rats by activating the PINK1/PARKIN signaling pathway, neuronal apoptosis was reduced and neuronal damage were improved in IS rats.

OBJECTIVE To establish a content determination method for multiple components in Sophora flavescens from different origins and to evaluate its quality by combining with chemometrics. METHODS Thirteen batches （No. K1-K13） of S. flavescens from different origins were selected as test samples. A high-performance liquid chromatography-tandem triple quadrupole mass spectrometry （HPLC-MS/MS） method was established to determine the contents of 12 components， including matrine， oxymatrine， betaine， cytisine， N-methylcytisine， sophoridine， genistein， sophoricoside， sophorone， formononetin， sophorolone Ⅰ and norkurarinone in S. flavescens. Chromatographic separation was performed on a Shim-pack GIST-HP C18 column with a mobile phase consisting of methanol （A） and water containing 0.1% formic acid （B）， using gradient elution at a flow rate of 0.25 mL/min， column temperature of 35 ℃， and an injection volume of 3 μL. Mass spectrometry was conducted using an electrospray ionization source with positive and negative ion scanning. Data were collected in segments using the multiple reaction monitoring mode. Technique for order preference by similarity to ideal solution （TOPSIS） and grey relational analysis （GRA）methods were employed to compare and comprehensively evaluate the 13 batches of S. flavescens from different origins. RESULTS The methodological validation for the content determination met the relevant regulatory requirements. The contents of the 12 components were 490.66-1 231.00， 11 088.10- 18 021.50， 7.91-25.38， 903.97-1 713.64， 336.08-1 485.54，1 065.33-2 075.50， 27.52-71.80， 109.36-517.83， 6 034.55-10 632.73， 21.26-145.35， 814.84-1 911.32， 1 040.87-3 446.37 μg/g）， respectively. TOPSIS results showed that the top 7 samples in Euclidean distance ranking were K6， K12， K11， K3， K5， K10， K13. The GRA results showed that the top 7 samples in the relative correlation ranking were K12， K11， K10， K6， K13， K5， K3. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate， highly sensitive， stable and reliable. Combined with chemometrics methods， it can be used for the quality control and evaluation of S. flavescens. The comprehensive quality of samples K3， K5， K6（ from Hebei）， K10（ from Sichuan）， K11-K13（ from Shanxi）， etc. is relatively superior.

Objective To investigate the gene expression and regulatory mechanisms of mouse embryonic fibroblasts (MEFs) under inflammatory conditions, aiming to elucidate the role of MEFs in inflammatory responses and provide a foundation for discovering anti-inflammatory drugs that act by modulating MEF function. Methods MEFs cultured in vitro were divided into the following groups: lipopolysaccharides (LPS)-treated group, inflammatory conditioned medium (CM)-treated group, and control group, which were treated with LPS, CM, and equal volume solvent, respectively. Transcriptome sequencing was used to analyze the effects of two stimuli on gene expression profile of MEFs. Real time fluorescence quantitative PCR (RT-qPCR) was employed to verify the transcription levels of highly expressed genes of MEFs induced by CM. ELISA was performed to determine the concentrations of cytokines in cell supernatants. Finally, the regulatory effects of CM on the activation of signaling pathways in MEFs were analyzed by immunoblotting. Results Transcriptome analysis showed that both LPS and CM induced the transcription of a large number of genes in MEFs. Compared with LPS, CM potentiated the mRNA transcription of some acute phase proteins, inflammatory cytokines, chemokines, matrix metalloproteinases (MMP), prostaglandin synthetases, and colony-stimulating factors. The transcriptome analysis was verified by RT-qPCR. The results of ELISA showed that CM treatment significantly increased the secretion of interleukin 6 (IL-6), C-C motif chemokine ligand (CCL2), and C-X-C motif chemokine ligand (CXCL1) by MEFs compared with LPS. Mechanism study showed that both LPS and CM induced the phosphorylation of nuclear factor-κB p65 (NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), extracellular regulated protein kinases 1/2 (ERK1/2), and TANK-binding kinase (TBK) in MEFs, and CM strongly stimulated the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in MEFs. Conclusion Both LPS and CM can induce transcription and protein secretion of various inflammation-related genes in MEFs. CM can partly enhance LPS-induced activation of MEFs, and the mechanism may be related to the enhancement effect of CM on the activation STAT3 signaling pathway.
Animals ; Fibroblasts/immunology* ; Mice ; Lipopolysaccharides/pharmacology* ; Inflammation/metabolism* ; Signal Transduction/drug effects* ; Gene Expression Regulation/drug effects* ; Cytokines/genetics* ; Culture Media, Conditioned/pharmacology* ; Cells, Cultured

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Science and technology evaluation plays an important role in improving the hospital's science and technology innovation capabilities and academic discipline construction.The global Cardiovascular Academic Performance Evaluation(CAPE)system focuses on the development of cardiovascular specialties in hospitals,emphasizing the evaluation of international academic performance of cardiovascular specialties,and delving into the sub-specialty of cardiovascular diseases.CAPE system contributes to pioneering preliminary explorations in literature searching strategies,data standardization,disciplinary definitions and other aspects.

Objective:To develop and verify a nomogram to predict disease-free survival(DFS)and overall survival(OS)for patients undergoing cervical cancer surgery,which may provide reference for evaluating the prognosis of cervical cancer patients undergoing surgery.Methods:The clinical,pathological and follow-up data of patients who underwent radical operation for cervical cancer in Xijing Hospital,Air Force Medical University from March 2013 to October 2018 were analyzed retrospectively.Based on Cox regression analysis,Bayesian Informa-tion Criterion(BIC)backward stepwise selection method and R square screening variables,Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI)were used to compare the predictive efficiency of the model,and a nomogram with better predictive efficiency was selected.The consistency index(C-index)and the receiver operating characteristic curve(ROC)were used to test the efficiency of the nomogram.Results:A total of 950 patients with cervical cancer were enrolled in this study.The risk factors for constructing the DFS nomogram were FIGO stage(2018),parametrium invasion,invasion depth,and maximum tumor diameter.The C-index for DFS in the training cohort and the verification cohort were 0.754 and 0.720,respectively.The area under ROC of the training cohort for 1-,3-and 5-years was 0.74(95%CI 0.65-0.82),0.77(95%CI 0.71-0.83)and 0.79(95%CI0.74-0.85),and the areas under ROC of verification cohort 1-,3-and 5-years were 0.72(95%CI 0.58-0.87),0.75(95%CI 0.64-0.86)and 0.72(95%CI 0.61-0.84),respectively.The risk factors for con-structing the OS nomogram were FIGO stage(2018),histological type,LVSI,parametrium invasion,surgical mar-gin,and invasion depth.The C-index for OS in the training cohort and the verification cohort were 0.737 and 0.759,respectively.The area under ROC of the 3-and 5-year training cohort were 0.76(95%CI 0.69-0.83)and 0.78(95%CI 0.72-0.84),and the areas under ROC of verification cohort 3-and 5-years were 0.76(95%CI 0.65-0.87)and 0.79(95%CI 0.69-0.88),respectively.Conclusions:This study is based on real-world big data to construct nomogram of DFS for 1,3,and 5 years and OS for 3,and 5 years for cervical cancer,which have ideal predictive effects and help clinical physicians correctly evaluate the prognosis of cervical cancer surgery patients.It provides strong reference basis for diagnosis,treatment,and prognosis evaluation.

【Objective】 To explore how to identify rare unexpected antibodies using routine serology methods in blood transfusion department of grassroots hospitals. 【Methods】 A patient with gastrointestinal bleeding with inconsistent forward and reverse blood typing, positive antibody screening and incompatible blood matching in our hospital was selected as the research object. Mixed human O cell absorption method was used for blood type identification, and 10-panel reagent red blood cells, manual polybrene test, 2-mercaptoethanol(2-ME) test, blind match and pedigree study were used to explore the antibody characteristics. 【Results】 The serological test results of the patient′s serum were as follows: The blood group was type B and RhD positive, and negative for direct antiglobulin test; The antibody was IgM; The likelihood of this antibody being anti-s, anti-Fy^a or anti-k was low, and compound antibodies could not be excluded; The blood of the patient did not match with blood samples of 20 blood donors in the major side, while it matched with all the blood samples of her three sisters. 【Conclusion】 When the antibodies of high-prevalence antigen series in plasma cannot be identified, the matched blood may be found tthrough family survey for irradiation and transfusion.

Objective To study the effect of low concentrations of sodium fluoride on the osteogenic/odontogenic differentiation of human dental pulp cells(hDPCs)in vitro.Methods This study was reviewed and approved by the Ethics Committee.hDPCs were cultured using a modified tissue explant technique in vitro.The effects of different con-centrations of sodium fluoride on the proliferation of hDPCs were measured by methylthiazol tetrazolium(MTT)assay.Appropriate concentrations were added to the osteogenic/odontogenic differentiation induction medium,and the cells were induced in vitro.Alizarin red S staining was used to detect the osteoblastic/odontogenic differentiation ability of the cells,and the mRNA expression of the key differentiation factors was detected by RT-qPCR.Moreover,the expres-sion of key molecules of endoplasmic reticulum stress(ERS)was detected by RT-qPCR and Western blot.The data were analyzed with the SPSS 18.0 software package.Results Low concentration of NaF(0.1 mmol/L)could stimulate cell proliferation in vitro,while a high concentration(5-10 mmol/L)could inhibit cell proliferation(P＜0.05).According to the literature and the experimental data,0.1 mmol/L NaF was selected as the following experimental concentration.The levels of alizarin red S staining were increased after NaF induction of mixed osteogenic/odontogenic differentiation in vi-tro.The mRNA expression levels of key molecules for osteogenic/odontogenic differentiation,dentin sialophosphoprotein(DSPP),bone sialoprotein(BSP)and osteocalcin(OCN),were increased(P＜0.05).The mRNA levels of ERS markers(splicing x-box binding protein-1(sXBP1),glucose-regulated protein 78(GRP78)and activating transcription Factor 4(ATF4)were increased in NaF-treated cells.The protein expression levels of key ER stress molecules(phosphorylated RNA-activated protein kinase-like ER-resident kinase(p-PERK),phosphorylated eukaryotic initiation factor-2α(p-eIF2α)and ATF4)were higher in NaF-treated cells.Conclusion A low concentration of NaF promotes the osteogenic/odontogenic differentiation of hDPCs and increases the level of ER stress.

BACKGROUND:Studies have found that glucagon-like peptide-1 and its analogues have a significant neuroprotective effect,and some drugs have been applied to the clinical stage Ⅲ study of Alzheimer's disease.However,the mechanism of its neuroprotective effect is still unclear,which needs to be further explored and clarified. OBJECTIVE:To screen out the genes related to the pathogenesis of Alzheimer's disease and the related targets of semaglutide for the treatment of Alzheimer's disease based on bioinformatics and network pharmacology analyses,to identify the potential target genes by comprehensive analysis of the two and to verify them at the cellular level. METHODS:Using DisGeNET database,differentially expressed genes between Alzheimer's disease patients and healthy population were screened out.The chemical structure formula and two-dimensional structure diagram of semaglutide were obtained using PubChem online database.GO/KEGG enrichment analysis was performed using DAVID online database.A protein-protein interaction network was constructed by using the STRING database.The HPA database was used to determine the distribution characteristics of the target proteins in various human tissues.Finally,western blot was used to detect relevant protein expression in HT22 cells after semaglutide intervention. RESULTS AND CONCLUSION:With the dataset in DisGeNET database,3 374 differentially expressed genes between Alzheimer's disease patients and healthy people were obtained,and meanwhile,101 target genes of semaglutide potential drugs were obtained.There were 23 intersection genes between them.Ten key genes were identified based on the protein-protein interaction network,which were silent information regulator 1(SIRT1),CASP9,CCND1,CASP1,KEAP1,DLG4,CASP4,GRB2,GRIA1,and EDNRA.The results of GO gene functional annotation analysis of key genes showed that the positive regulatory activity of cysteine endopeptidase,the positive regulation of proteolysis,and the positive regulation of cysteine endopeptidase involved the cytoplasmic part of the apoptotic activity process;AMPA glutamate receptor complex,inflammatory complex,CARD domain binding,cysteine endopeptidase activity,and cysteine endopeptidase activity were involved in the apoptotic process.The results of KEGG signaling pathway analysis indicated that colorectal cancer,non-small cell carcinoma,and endometrial carcinoma were related to immune infiltration,inflammation and autophagic apoptosis.In addition,according to the association ranking of key genes and their distribution in different tissues of HPA online database,SIRT1 was identified as the most significant differential gene.The expression level of SIRT1 protein was significantly down-regulated in HT22 cells after β-amyloid protein 1-42 treatment,but it could be significantly increased after being treated with semaglutide.To conclude,SIRT1 may be a target gene for semaglutide in the treatment of Alzheimer's disease.