OBJECTIVE To investigate the potential mechanism of berberine improving diabetes mellitus type 2 （T2DM） combined with metabolic-associated fatty liver disease （MAFLD） by regulating ceramide. METHODS Thirty-two db/db mice with blood glucose levels＞11.1 mmol/L （T2DM model） were divided into four groups： model group， berberine low- and high-dose groups [100， 200 mg/（kg·d）] and metformin group [300 mg/（kg·d）]， with 8 mice in each group. Additionally， 8 wt/wt mice were selected as the normal control group. Mice in each group were administered the corresponding drug solution or water by gavage once daily for a continuous period of 6 weeks. During the experiment， the body weight of the mice was monitored， and the differences in final body weight were analyzed. After the last administration， the body shape of the mice in each group was observed， and their fasting blood glucose （FBG） and the lipid indicators [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] were measured. Fasting serum insulin （FINS） levels were also measured， and the insulin resistance index HOMA-IR） and insulin sensitivity index （ISI） were calculated. Liver weight， liver index and serum liver function indicators [alanine transaminase （ALT）， aspartate transaminase（AST）] were assessed， and hepatic histopathological changes were observed. Additionally， the expression of fatty acid synthesis-related proteins [sterol regulatory element-binding protein 1 （SREBP1）， fatty acid synthase （FASN）， acetyl-CoA carboxylase 1 （ACC1）] in liver tissue was examined. Serum samples from the normal control group， model group， and berberine high-dose group were collected for non-targeted lipidomics analysis and validation. RESULTS Compared with the model group， the pathological changes， including disordered liver tissue cell arrangement and lipid vacuoles， were significantly improved in the berberine low- and high-dose groups. The significant decreases or down-regulations were observed in body weight in the last week， as well as FBG， TC， TG， and LDL-C levels， HOMA-IR （except for the berberine low-dose group）， liver weight， liver index， AST and ALT levels， and protein expressions of SREBP1， FASN and ACC1. Additionally， HDL-C levels， FINS （except for the berberine high-dose group）， and ISI （except for the berberine low-dose group） were significantly increased （P＜0.05）. A total of 21 potential differential metabolites， including multiple types of ceramides， were identified； these metabolites were primarily enriched in sphingolipid metabolism and glycerophospholipid metabolism pathways. Verification experiments confirmed that high-dose berberine significantly reduced the serum content of ceramide in model mice （P＜0.05）. CONCLUSIONS Berberine reduces insulin resistance， improves liver damage and lipid accumulation in the T2DM combined with MAFLD mice， and these effects may be related to the reduction of ceramide content.

BACKGROUND:Polyamines play a crucial role in tissue calcification.Spermidine/spermine N1-acetyltransferase 1(SAT1),as a key rate-limiting enzyme regulating intracellular polyamine metabolism,has been associated with various pathological processes.However,its role in vascular calcification remains unclear.OBJECTIVE:To investigate the role of SAT1 in rat vascular smooth muscle cell calcification.METHODS:(1)Bioinformatics analysis:Differential expression of SAT1 in human carotid atherosclerotic plaques and their surrounding healthy carotid artery tissues were using GEO datasets.PanglaoDB database was used to analyze SAT1 expression abundance and localization across different cell types through single-cell sequencing.(2)Rat vascular smooth muscle cells were divided into three groups:a control group cultured in DMEM medium,a calcification group induced by DMEM medium containing 10 mmol/L β-glycerophosphate sodium and 3 mmol/L calcium chloride,and the 50,100 μmol/L diacetylaminotriazamidine groups treated with the SAT1 inhibitor,diacetylaminotriazamidine,in addition to the calcification medium.After 7-10 days of culture,alizarin red S staining was performed,and cellular calcium content and alkaline phosphatase activity were assessed.Western blot was used to detect the protein expression of Runt-related transcription factor 2,bone morphogenetic protein 2,alpha-smooth muscle actin,and SAT1.Immunofluorescence staining was conducted to examine the expression of Runt-related transcription factor 2 and SAT1.RESULTS AND CONCLUSION:(1)Bioinformatics analysis revealed significantly upregulated expression of SAT1 and Runt-related transcription factor 2(P<0.05)in carotid atherosclerotic plaques compared with healthy carotid tissues(P<0.05).Single-cell sequencing database analysis confirmed SAT1 expression in vascular smooth muscle cells.(2)Compared with the control group,the calcification group showed significantly increased Runt-related transcription factor 2,bone morphogenetic protein 2,SAT1,calcium content,and alkaline phosphatase activity,while alpha-smooth muscle actin expression was significantly decreased(all P<0.05).Compared with the calcification group,the 50 and 100 μmol/L diacetylaminotriazamidine groups showed significantly decreased Runt-related transcription factor 2,bone morphogenetic protein 2,calcium content,and alkaline phosphatase activity,while alpha-smooth muscle actin expression was significantly increased(all P<0.05).(3)Immunofluorescence experiments demonstrated that compared with the calcification group,the expression intensity of Runt-related transcription factor 2 was significantly reduced in the 50 and 100 μmol/L diacetylaminotriazamidine groups.Overall,SAT1 may promote vascular smooth muscle cell calcification by upregulating Runt-related transcription factor 2 expression.

BACKGROUND:Polyamines play a crucial role in tissue calcification.Spermidine/spermine N1-acetyltransferase 1(SAT1),as a key rate-limiting enzyme regulating intracellular polyamine metabolism,has been associated with various pathological processes.However,its role in vascular calcification remains unclear.OBJECTIVE:To investigate the role of SAT1 in rat vascular smooth muscle cell calcification.METHODS:(1)Bioinformatics analysis:Differential expression of SAT1 in human carotid atherosclerotic plaques and their surrounding healthy carotid artery tissues were using GEO datasets.PanglaoDB database was used to analyze SAT1 expression abundance and localization across different cell types through single-cell sequencing.(2)Rat vascular smooth muscle cells were divided into three groups:a control group cultured in DMEM medium,a calcification group induced by DMEM medium containing 10 mmol/L β-glycerophosphate sodium and 3 mmol/L calcium chloride,and the 50,100 μmol/L diacetylaminotriazamidine groups treated with the SAT1 inhibitor,diacetylaminotriazamidine,in addition to the calcification medium.After 7-10 days of culture,alizarin red S staining was performed,and cellular calcium content and alkaline phosphatase activity were assessed.Western blot was used to detect the protein expression of Runt-related transcription factor 2,bone morphogenetic protein 2,alpha-smooth muscle actin,and SAT1.Immunofluorescence staining was conducted to examine the expression of Runt-related transcription factor 2 and SAT1.RESULTS AND CONCLUSION:(1)Bioinformatics analysis revealed significantly upregulated expression of SAT1 and Runt-related transcription factor 2(P<0.05)in carotid atherosclerotic plaques compared with healthy carotid tissues(P<0.05).Single-cell sequencing database analysis confirmed SAT1 expression in vascular smooth muscle cells.(2)Compared with the control group,the calcification group showed significantly increased Runt-related transcription factor 2,bone morphogenetic protein 2,SAT1,calcium content,and alkaline phosphatase activity,while alpha-smooth muscle actin expression was significantly decreased(all P<0.05).Compared with the calcification group,the 50 and 100 μmol/L diacetylaminotriazamidine groups showed significantly decreased Runt-related transcription factor 2,bone morphogenetic protein 2,calcium content,and alkaline phosphatase activity,while alpha-smooth muscle actin expression was significantly increased(all P<0.05).(3)Immunofluorescence experiments demonstrated that compared with the calcification group,the expression intensity of Runt-related transcription factor 2 was significantly reduced in the 50 and 100 μmol/L diacetylaminotriazamidine groups.Overall,SAT1 may promote vascular smooth muscle cell calcification by upregulating Runt-related transcription factor 2 expression.

AIM:This study explores how the combination of rapamycin(Rapa)and flagellin(FliC)affects the inhibition of 4T1 breast cancer cells.The approach involves using mRNA high-throughput sequencing to examine the underlying mechanisms of this combination therapy in vitro.METHODS:4T1 breast cancer cells were divided into four groups:control group,Rapa group,FliC group,and Rapa+FliC group.The changes in cell viability and apoptosis were detected by the CCK-8 method and flow cytometry.Concurrently,the KEGG pathway of differentially expressed genes(DEGs)was analyzed by high-throughput mRNA sequencing.Furthermore,the DEGs between the Rapa+FliC group and Rapa groups were analyzed using STRING.The PPI network of DEGs was then constructed,and the Hub genes were sub-sequently screened.The protein expression of the Hub gene was verified based on the HPA database.RESULTS:CCK-8 assays and flow cytometry analysis revealed that the combination of Rapa and FliC significantly increased both the inhibi-tion and apoptosis rates in 4T1 breast cancer cells compared to the rates observed with Rapa or FliC alone(P<0.05).Transcriptome sequencing indicated 579 DEGs between the Rapa group and the control group,predominantly in the PI3K/Akt signaling pathway.In contrast,DEGs between the FliC group and control were mainly concentrated in signaling path-ways like NOD-like receptor signaling.Additionally,150 DEGs were identified between the Rapa+FliC group and the Ra-pa group,focusing primarily on pathways such as mTOR.From the protein-protein interaction(PPI)network,ten hub genes,including Atm and Itga2,were identified.CONCLUSION:The combination of Rapa+FliC could inhibit the via-bility of 4T1 breast cancer cells in vitro and promote apoptosis,potentially through the PI3K/Akt/mTOR signaling path-way.The genes Atm and Itga2 could be pivotal in mediating the joint effect of this combination therapy.

Objective To investigate the current status of military training injuries among aviation cadets in a university,analyze the influencing factors and propose prevention and control measures.Methods Enrolled in the study in December 2021 were 605 male aviation cadets,of whom 192 were freshmen,202 were sophomores and 211 were juniors.A self-made questionnaire form was developed and used to investigate and analyze the occurrence of training injuries among aviation cadets.Results The rate of training injuries among the aviation cadets was 57.19%,of whom 43.75%were freshmen,60.40%were sophomores,and 66.35%were juniors.Injuries sites were mainly in the lower extremities,with freshmen,sophomores and juniors ranking the first,but with a decreasing trend.In injury-causing subjects,3 000 m race ranked the first in the freshmen,single parallel bars ranked the first in the sophomores,other factors ranked the first in the juniors.In terms of medical care,self-diagnosis and care accounted for 34.97%and outpatient medical care accounted for 46.82%,with the sum of them accounting for 81.79%.Conclusion There is a relatively high rate of training injuries among aviation cadets.The number of training injuries,affected injury sites,injury-causing subjects,onset of seasons and adverse factors vary with the advance of grades and display various features.Further emphasis on health education among aviation cadets and the improvement of outpatient medical service are of great importance to the prevention and treatment of training injuries among aviation cadets.

Lipid Droplets/metabolism* ; Bacteria ; Lipid Metabolism

Objective: To investigate oral health related life quality and associated factors of senior primary school students in Bengbu City, so as to provide scientific basis for targeted oral health education for children. Methods: A stratified cluster random sampling method was adopted to select 1 760 senior students (grade 5 to 6) from 12 primary schools in 4 districts of Bengbu City from September to November 2022. A cross sectional survey was conducted on the oral health of students through questionnaires related to oral health. The effect of oral problems on quality of life was assessed by the Child Daily Life Oral Influence Scale (Child-OIDP). Chi square test, non parametric test and binary Logistic regression model were used to analyze the influencing factors of oral health related quality of life in senior primary school students. Results: The prevalence of oral problems affecting the quality of daily life was 70.00%, and the severe impact rate was 15.06%. Oral feeding was the most affected (57.95%). The Child-OIDP score was (7.49±8.57). Binary Logistic regression analysis showed that mother s education level, self rated teeth and oral conditions, bruised tooth, toothache in the past year, and gingival bleeding in the past 2 weeks were significantly associated with the incidence of Child-OIDP ( OR=1.86-5.00, P <0.05). Conclusion It is common that oral problems affect the quality of daily life of senior primary school students in Bengbu. Families and schools should strengthen oral health knowledge education and behavior guidance, so as to reduce the impact of oral problems on daily life among senior primary school students.

Ambystoma mexicanum/immunology* ; Amputation ; Animals ; Biomarkers/metabolism* ; Blastomeres/immunology* ; Cell Lineage/immunology* ; Connective Tissue Cells/immunology* ; Epithelial Cells/immunology* ; Forelimb ; Gene Expression ; High-Throughput Nucleotide Sequencing ; Humans ; Immunity ; Peroxiredoxins/immunology* ; Regeneration/immunology* ; Regenerative Medicine/methods* ; Single-Cell Analysis/methods*

This study was aimed to prepare tripterine-coix seed component microemulsions (TCC-MEs) with coix seed oil and coix seed polysaccharide as bimodal excipients and evaluate its activity on anti-lung cancer in vivo.Coix seed oil was extracted by supercritical extraction methods and coix seed polysaccharide was obtained through hot water extraction and alcohol precipitation from coix seed.Then,coix seed oil was used as the oil phase,and coix seed polysaccharide aqueous solution was used as the aqueous phase.RH40 was used as the surfactant.PEG400 was used as cosurfactant to prepare microemulsion.TCC-MEs were made by water titration method and characterized by size,polymer dispersity index (PDI),zeta potential,encapsulation efficiency and drug loading capacity.And then,anti-tumor activity of TCC-MEs was evaluated on the xenograft Lewis tumor mouse models.The liver and kidney toxicity was evaluated by HE staining and biochemical indicators.The results showed that the optimized prescription for TCC-MEs was coix seed oil 400 mg,RH40 300 mg,PEG 400 100 mg,coix seed polysaccharide 50 mg,tripterine 10 mg;and the tripterine encapsulation efficiency was (90.72 ± 0.28)％;the drug loading capacity was (1.08 ± 0.17)％;the mean diameter of microemulsion was (43.86 ± 0.22) nm;PDI was 0.10 ± 0.01;the zeta potential was (-13.14 ± 1.35) mV.The activity of anti-lung cancer in TCC-MEs was significantly better than that of the control group,with no significant liver and kidney toxicity after treatment with TCC-MEs.It was concluded that the prepared TCC-MEs had advantages of small amount of conventional auxiliary materials,small particle size and high stability.This study showed that the combination of triptolide and coix seed to microemulsion system has synergistic and attenuated effect.

Objective To analyze effect of perioperative holistic nursing for benign breast tumor patients with Mammotome minimally invasive treatment.Methods A total of 90 patients with benign breast tumors in our hospital receiving the Mammotome treatment were divided into the observation group and the control group according to a random number table method,with 45 cases in each group.Observation group was given holistic nursing intervention,and the control group was treated with general nursing intervention.Anxiety and depression scores,surgery and hospital stay,complications and quality of life score were compared.Results Before treatment,anxiety and depression scores of two groups showed no significant difference (P ＞ 0.05);After nursing,anxiety and depression scores were decreased,but observation group were lower than the control group,the difference was statistically significant (P ＜ 0.05);Complication rate in the observation group was lower,surgery and hospital stay were shorter,and average quality of life score was significantly higher than the control group,the differences were statistically significant (P ＜ 0.05).Conclusion Perioperative nursing intervention can improve anxiety and depression,reduce the incidence of complications,shorten operative time and hospitalization time,and improve the quality of life of benign breast tumor patients with Mammotome minimally invasive treatment.