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.

Objective:To retrieve, evaluate and summarize the best evidence for the assessment and non-pharmacological management of chemotherapy-induced peripheral neuropathy.Methods:The literature related to the assessment and non-pharmacological management of chemotherapy-induced peripheral neuropathy was systematically searched from January 1, 2018 to December 4, 2023 in clinical decision support systems, guideline networks, databases and related society websites at home and abroad, including clinical decision-making, guidelines, expert consensus, evidence summary, systematic review, and randomized controlled studies. Four reviewers evaluated the quality of the included studies and extracted evidence.Results:A total of 18 articles were included, including 1 clinical decision, 2 guidelines, 3 expert consensuses, 5 evidence summaries, 4 systematic reviews, and 3 randomized controlled studies. A total of 21 pieces of evidence were summarized from 7 items: assessment, exercise therapy, acupuncture therapy, cryotherapy, compression therapy, health education, and multidisciplinary diagnosis and treatment.Conclusions:Non-pharmacological intervention is an effective means to improve chemotherapy-induced peripheral neuropathy. Medical personnel should combine professional judgment with patient′s will, prudently, wisely and clearly use the best evidence to prevent or reduce chemotherapy-induced peripheral neuropathy and improve patients′ quality of life.

Objective:To explore the potential relationship between sugar metabolism,acid production and cariogenicity of Prevotella denticola.Methods:Morphological features of Prevotella denticola were observed and respectively cultured under incubation conditions with and without sugar and at different pH values.The growth characteristics of Prevotella denticola were detected by UV-Vis spectro-photometer and pH meter,the organic acid content in the culture supernatants of the cultures was detected by HPLC.Dentin slices were divided into control group,phosphoric acid group and the Prevotella denticola group and cultured in the corresponding mediu for 1 and 2 weeks respectively,the degree of demineralization of the samples was examined SEM and VHM.Results:Prevotella denticola fermen-ted sucrose and glucose,produced acids with its final pH values as low as 4.7,Succinic acid and acetic acid were its main metabolites.Prevotella denticola was moderately acid-tolerant.Furthermore,Prevotella denticola was able to cause dentin demineralization,and the Vickers hardness value of dentin samples in the Prevotella denticola group was significantly decreased compared with the control group(P＜0.05).Conclusion:The cariogenic capacity of Prevotella denticola may be related to its sugar metabolism and acid production.

OBJECTIVE To study and analyze the relationship between serum levels of Endocan,Cyclophilic A (CyPA),and asprosin with the condition severity and cognitive function in patients with obstructive sleep apnea hypopnea syndrome(OSAHS). METHODS From November 2021 to December 2023,99 OSAHS patients who visited our hospital were collected and separated into mild group(n=29),moderate group(n=45),and severe group(n=25) based on the apnea hypopnea index(AHI). ELISA method was applied to detect serum levels of Endocan,CyPA,and asprosin. Multivariate logistic regression was used to analyze the influencing factors of severity of condition. ROC curve was plotted to analyze the diagnostic value of serum Endocan,CyPA,and asprosin for cognitive function in OSAHS patients. Spearman rank correlation was applied to analyze the correlation between serum Endocan,CyPA,asprosin,with severity of condition,cognitive function. RESULTS Compared with the mild group,the serum levels of Endocan,CyPA,and asprosin were obviously increased in the moderate and severe groups(P<0.05),and the serum levels of Endocan,CyPA,and asprosin in the severe group were obviously increased compared to the moderate group(P<0.05). There were statistically obvious differences in AHI,Epworth sleepiness scale(ESS) scores,and some sleep related parameters among the three groups(P<0.05). Further analysis revealed that mean blood oxygen saturation(MSaO2) was a protective factor affecting the severity of condition(P<0.05),while AHI,serum Endocan,CyPA,and asprosin levels were all risk factors affecting the severity of condition(P<0.05). The serum levels of Endocan,CyPA,and asprosin in patients with cognitive impaired were obviously higher than those in patients with normal cognition,and the MoCA score was lower than that in patients with normal cognition(P<0.05). The AUC of serum Endocan,CyPA,asprosin,and combined diagnosis for cognitive impairment in patients was 0.889,0.893,0.861,and 0.974,respectively,and the combined diagnosis was obviously better than individual diagnosis of Endocan(Z=2.832,P=0.005),CyPA(Z=2.907,P=0.004),and asprosin(Z=3.225,P=0.001). Serum Endocan,CyPA,and asprosin were positively correlated with AHI and negatively correlated with MoCA score(P<0.05). CONCLUSION In patients with severe OSAHS and cognitive impairment,serum Endocan,CyPA,and asprosin levels are all increased,and they have certain auxiliary diagnostic value for the severity of condition and cognitive function.

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.