Objective To explore the shared mechanisms of genes related to three common chronic diseases non-alcoholic fatty liver disease(NAFLD),type 2 diabetes mellitus(T2DM)and atherosclerosis(AS)with ageing as well as potential therapeutic agents by using bioinformatics analysis,machine learning algorithms and molecular docking methods and techniques.Methods Ageing-related genes were collected and organized from AgeingAtlas,CellAge,GenAge,and MSigDB databases.After taking the intersection of genes related to NAFLD,T2DM and AS obtained from databases such as CTD,DisGeNET,GeneCards,OMIM,PharmGKB,and TTD and the gene sets obtained based on the GEO differential gene analysis,we obtained the set of related disease genes for these three common chronic diseases.The KEGG pathway enrichment analysis was performed on the ageing gene set and the three disease-related gene sets using the clusterProfiler package,and the intersection was taken.The enriched genes in the KEGG pathway were merged and imported into the STRING database;the PPI network was constructed.We analyzed the core sub-modules in the PPI network using the MCODE tool and calculated the essential values of Nim and Cim for each node and module.Meanwhile,three machine learning models were used to screen the feature genes:the Lasso regression model,the Boruta algorithm,and the random forest model.The HIT2.0 database was utilized to find the targeted TCM small molecules related to the key feature genes.Small molecules were evaluated and analyzed by ADMET using SwissADME and ADMETlab 3.0 online system.The molecular docking method was utilized to dock the key action targets and screen small molecules.Results A total of 1 325,616,78,and 597 genes related to ageing,NAFLD,T2DM,and AS were obtained.The KEGG pathway enrichment analysis results for ageing and the three diseases were taken to intersect to get two shared intersecting pathways containing 243 genes.The PPI network was constructed,and Cluster 2 had the highest Cim value among the three core submodules.According to the results of signature gene screening,combined with PPI network module analysis results,four signature genes related to ageing were found:CDK6,CDKN1A,MYC,and PTEN.These four targets have 94 potential TCM small molecule candidates,among which resveratrol(RSV)is a TCM small molecule common to these four targets.The ADMET evaluation showed that it had good drug-forming properties.The PTEN target had a high Nim value,and molecular docking of RSV with PTEN showed good binding stability.Conclusion A potential herbal small molecule,RSV,was identified from the perspective of ageing,which may prevent and treat three common chronic diseases,namely,NAFLD,T2DM and AS,by regulating the key gene PTEN.

Objective : To establish an interleukin-1β (Il-1β) induced inflammatory model of rat articular chondro- cytes (ACs) , and to investigate the relationship between the expression of lysine acetyltransferase 7 (KAT7) under inflammatory stimulation and the senescence of ACs. Methods: Primary ACs were obtained by digestion of rat knee cartilage with collagenase type Ⅱ and identified. The inflammatory model of ACs was induced by IL-1β . KAT7 was over-expressed or knocked down in ACs by adeno-associated virus infection or small interfering RNA transfection , respectively. A negative control group was set up. Transwell assay was used to detect cell migration ability. Senes- cent cells were stained with senescence-associated β-galactosidase (SA-β-Gal) . Western blot ( WB) was used to detect the protein expression levels of KAT7 , collagen type II (Col Ⅱ ) , matrix metalloproteinase 13 (MMP13) , tumor protein p53 (p53) and cyclin-dependent kinase inhibitor 1A (p21) . The cells of negative control group and KAT7 over-expression group were performed for RNA sequencing , and WB was used to verify the related signaling pathways obtained by Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. Results: Compared with the control group , the SA-β-Gal staining was enhanced , the protein expression of Col Ⅱ decreased , the pro- tein expression of MMP13 and p53 increased , the cell migration ability decreased , and the expression of KAT7 also increased in the ACs of rats after IL-1β stimulation. Compared with the negative control group , the SA-β-Gal stai- ning was enhanced , the protein expression of Col Ⅱ decreased , the protein expression of MMP13 , p53 and p21 in- creased , and the cell migration ability decreased in the KAT7 over-expression group. Compared with the negative control group , the SA-β-Gal staining was weakened , the protein expression of Col Ⅱ increased , the protein expres- sion of MMP13 , p53 and p21 decreased , and the cell migration ability was enhanced in the KAT7 knockdown inflammatory model of ACs. KEGG enrichment analysis showed that phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was activated. Compared with the negative control group , the relative protein ex⁃pression levels of phosphorylated protein kinase B (p⁃AKT)/AKT and phosphorylated mammalian target of rapamy⁃cin (p⁃mTOR)/mTOR in KAT7 over⁃expression group increased. The relative protein expression levels of p ⁃AKT/AKT and p ⁃mTOR/mTOR in KAT7 knockdown cells decreased. Conclusion Rat ACs with high expression of KAT7 exhibit senescence and osteoarthritis phenotype , and the mechanism may be related to the activation of PI3K/AKT/mTOR signaling pathway by KAT7.

Objective To build an inpatient hospital discharge preparation service management platform,to explore its application outcomes,and to enhance the quality of discharge preparation service management.Methods A research team was set up,and the literature was referenced.The platform was built on the basis of connecting and optimizing various existing information systems in the hospital,including 6 modules:evaluation,implementation of nursing,referral,monitoring feedback,follow-up,and continued nursing.Patients admitted to a tertiary comprehensive hospital were conveniently selected as research subjects in Shandong Province from August 2023 to January 2024.The 97 patients included after the platform application(November 2023 to January 2024)were selected as an experimental group,and the 97 patients included before the platform application(August to October 2023)were selected as a control group.The rate of unplanned readmission within 30 days,the utilization rate of"Internet+Nursing Services",and the time for assessing the demand for discharge planning service were compared between the 2 groups.In addition,in February 2024,300 healthcare professionals from the same hospital were selected to evaluate their satisfaction with the use of the platform.Results There were 7 cases dropping out in each of the 2 groups.The rate of unplanned readmission within 30 days in the experimental group was lower than that in the control group;the utilization rate of"Internet+Nursing Services"was higher than that in the control group;the time for assessing the demand for discharge planning service was less than that in the control group,with statistically significant differences(P＜0.05).In the satisfaction survey of medical staff on the use of the platform,the effective questionnaire response rate was 94.67％,and the score of the clinical nursing information system effectiveness evaluation scale was(100.84±16.48)points.Conclusion The use of this platform can reduce the unplanned readmission rate of patients within 30 days,promote the development of"Internet+Nursing Services",reduce the time for assessing the needs of discharge planning services,and medical staff are highly satisfied with the use of the platform.

Colony-stimulating factor-1 receptor (CSF1R)-related leukoencephalopathy (CSF1R-L) is a rare autosomal dominant neurodegenerative disorder caused by mutations in the CSF1R gene. It is typically characterized by rapidly progressive cognitive decline, motor dysfunction, and psychiatric or behavioral abnormalities, leading to significant disability and early mortality. More than 100 mutations of CSF1R have been identified in CSF1R-L, but the clinical-genotype relationship is unclear. This report describes a case of CSF1R-L that initially presented with atypical symptoms of left lower limb pain, numbness, and weakness. Despite the non-specific presentation, comprehensive imaging data were available throughout the disease course. Genetic testing identified a heterozygous missense mutation in exon 18 of the CSF1R gene (c.2508CA, p.Ser836Arg), a novel variant not previously reported in the literature. This case offers valuable insights into the dynamic progression of cranial MRI changes in CSF1R-L, broadens the genetic spectrum of this disease, enhances awareness among clinicians, and provides crucial information for the early diagnosis of this condition.

Objective To explore the shared mechanisms of genes related to three common chronic diseases non-alcoholic fatty liver disease(NAFLD),type 2 diabetes mellitus(T2DM)and atherosclerosis(AS)with ageing as well as potential therapeutic agents by using bioinformatics analysis,machine learning algorithms and molecular docking methods and techniques.Methods Ageing-related genes were collected and organized from AgeingAtlas,CellAge,GenAge,and MSigDB databases.After taking the intersection of genes related to NAFLD,T2DM and AS obtained from databases such as CTD,DisGeNET,GeneCards,OMIM,PharmGKB,and TTD and the gene sets obtained based on the GEO differential gene analysis,we obtained the set of related disease genes for these three common chronic diseases.The KEGG pathway enrichment analysis was performed on the ageing gene set and the three disease-related gene sets using the clusterProfiler package,and the intersection was taken.The enriched genes in the KEGG pathway were merged and imported into the STRING database;the PPI network was constructed.We analyzed the core sub-modules in the PPI network using the MCODE tool and calculated the essential values of Nim and Cim for each node and module.Meanwhile,three machine learning models were used to screen the feature genes:the Lasso regression model,the Boruta algorithm,and the random forest model.The HIT2.0 database was utilized to find the targeted TCM small molecules related to the key feature genes.Small molecules were evaluated and analyzed by ADMET using SwissADME and ADMETlab 3.0 online system.The molecular docking method was utilized to dock the key action targets and screen small molecules.Results A total of 1 325,616,78,and 597 genes related to ageing,NAFLD,T2DM,and AS were obtained.The KEGG pathway enrichment analysis results for ageing and the three diseases were taken to intersect to get two shared intersecting pathways containing 243 genes.The PPI network was constructed,and Cluster 2 had the highest Cim value among the three core submodules.According to the results of signature gene screening,combined with PPI network module analysis results,four signature genes related to ageing were found:CDK6,CDKN1A,MYC,and PTEN.These four targets have 94 potential TCM small molecule candidates,among which resveratrol(RSV)is a TCM small molecule common to these four targets.The ADMET evaluation showed that it had good drug-forming properties.The PTEN target had a high Nim value,and molecular docking of RSV with PTEN showed good binding stability.Conclusion A potential herbal small molecule,RSV,was identified from the perspective of ageing,which may prevent and treat three common chronic diseases,namely,NAFLD,T2DM and AS,by regulating the key gene PTEN.

Objective To build an inpatient hospital discharge preparation service management platform,to explore its application outcomes,and to enhance the quality of discharge preparation service management.Methods A research team was set up,and the literature was referenced.The platform was built on the basis of connecting and optimizing various existing information systems in the hospital,including 6 modules:evaluation,implementation of nursing,referral,monitoring feedback,follow-up,and continued nursing.Patients admitted to a tertiary comprehensive hospital were conveniently selected as research subjects in Shandong Province from August 2023 to January 2024.The 97 patients included after the platform application(November 2023 to January 2024)were selected as an experimental group,and the 97 patients included before the platform application(August to October 2023)were selected as a control group.The rate of unplanned readmission within 30 days,the utilization rate of"Internet+Nursing Services",and the time for assessing the demand for discharge planning service were compared between the 2 groups.In addition,in February 2024,300 healthcare professionals from the same hospital were selected to evaluate their satisfaction with the use of the platform.Results There were 7 cases dropping out in each of the 2 groups.The rate of unplanned readmission within 30 days in the experimental group was lower than that in the control group;the utilization rate of"Internet+Nursing Services"was higher than that in the control group;the time for assessing the demand for discharge planning service was less than that in the control group,with statistically significant differences(P＜0.05).In the satisfaction survey of medical staff on the use of the platform,the effective questionnaire response rate was 94.67％,and the score of the clinical nursing information system effectiveness evaluation scale was(100.84±16.48)points.Conclusion The use of this platform can reduce the unplanned readmission rate of patients within 30 days,promote the development of"Internet+Nursing Services",reduce the time for assessing the needs of discharge planning services,and medical staff are highly satisfied with the use of the platform.

Colony-stimulating factor-1 receptor (CSF1R)-related leukoencephalopathy (CSF1R-L) is a rare autosomal dominant neurodegenerative disorder caused by mutations in the CSF1R gene. It is typically characterized by rapidly progressive cognitive decline, motor dysfunction, and psychiatric or behavioral abnormalities, leading to significant disability and early mortality. More than 100 mutations of CSF1R have been identified in CSF1R-L, but the clinical-genotype relationship is unclear. This report describes a case of CSF1R-L that initially presented with atypical symptoms of left lower limb pain, numbness, and weakness. Despite the non-specific presentation, comprehensive imaging data were available throughout the disease course. Genetic testing identified a heterozygous missense mutation in exon 18 of the CSF1R gene (c.2508CA, p.Ser836Arg), a novel variant not previously reported in the literature. This case offers valuable insights into the dynamic progression of cranial MRI changes in CSF1R-L, broadens the genetic spectrum of this disease, enhances awareness among clinicians, and provides crucial information for the early diagnosis of this condition.

Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth,known as taurodontism;thus,indicating the critical role of Wnt10a in tooth root morphogenesis.However,the endogenous mechanism by which epithelial Wnt10a regulates Hertwig's epithelial root sheath(HERS)cellular behaviors and contributes to root furcation patterning remains unclear.In this study,we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10afl/flmice from post-natal day 0.5(PN0.5)to PN4.5.EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial(IEE)cells of HERS in K14-Cre;Wnt10afl/flmice at PN2.5 and PN3.5.Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane,which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10afl/flmice.RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10afl/fl mice.Furthermore,after activation of Notch signaling in K14-Cre;Wnt10afl/flmolars by Notch2 adenovirus and kidney capsule grafts,the root furcation defect was partially rescued.Taken together,our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.