BACKGROUND: Senescent human skin primary fibroblast (FB) models have been established for studying aging-related, proliferative, and inflammatory skin diseases. The aim of this study was to compare the transcriptome characteristics of human primary dermal FBs from children and the elderly with four senescence models. METHODS: Human skin primary FBs were obtained from healthy children (FB-C) and elderly donors (FB-E). Senescence models were generated by ultraviolet B irradiation (FB-UVB), D-galactose stimulation (FB-D-gal), atazanavir treatment (FB-ATV), and replication exhaustion induction (FB-P30). Flow cytometry, immunofluorescence staining, real-time quantitative polymerase chain reaction, co-culturing with immune cells, and bulk RNA sequencing were used for systematic comparisons of the models. RESULTS: In comparison with FB-C, FB-E showed elevated expression of senescence-related genes related to the skin barrier and extracellular matrix, proinflammatory factors, chemokines, oxidative stress, and complement factors. In comparison with FB-E, FB-UVB and FB-ATV showed higher levels of senescence and expression of the genes related to the senescence-associated secretory phenotype (SASP), and their shaped immune microenvironment highly facilitated the activation of downstream immune cells, including T cells, macrophages, and natural killer cells. FB-P30 was most similar to FB-E in terms of general transcriptome features, such as FB migration and proliferation, and aging-related characteristics. FB-D-gal showed the lowest expression levels of senescence-related genes. In comparisons with the single-cell RNA sequencing results, FB-E showed almost complete simulation of the transcriptional spectrum of FBs in elderly patients with atopic dermatitis, followed by FB-P30 and FB-UVB. FB-E and FB-P30 showed higher similarity with the FBs in keloids. CONCLUSIONS Each senescent FB model exhibited different characteristics. In addition to showing upregulated expression of natural senescence features, FB-UVB and FB-ATV showed high expression levels of senescence-related genes, including those involved in the SASP, and FB-P30 showed the greatest similarity with FB-E. However, D-galactose-stimulated FBs did not clearly present aging characteristics.
Humans ; Fibroblasts/drug effects* ; Cellular Senescence/physiology* ; Skin/metabolism* ; Child ; Transcriptome/genetics* ; Aged ; Ultraviolet Rays ; Cells, Cultured ; Galactose/pharmacology*

Dental pulp-dentin complex defects remain a major unresolved problem in oral medicines. Clinical therapeutic methods including root canal therapy and vital pulp therapy are both considered as conservative strategies, which are incapable of repairing the pulp-dentin complex defects. Although biomaterial-based strategies show remarkable progress in antibacterial, anti-inflammatory, and pulp regeneration, the important modulatory effects of nerves within pulp cavity have been greatly overlooked, making it challenging to achieve functional pulp-dentin complex regeneration. In this study, we propose an injectable bioceramics-containing composite hydrogel in combination of Li-Ca-Si (LCS) bioceramics and gelatin methacrylate matrix with photo-crosslinking properties. Due to the sustained release of bioactive Li, Ca and Si ions from LCS, the composite hydrogels possess multiple functions of promoting the neurogenic differentiation of Schwann cells, odontogenic differentiation of dental pulp stem cells, and neurogenesis-odontogenesis couples in vitro. In addition, the in vivo results showed that LCS-containing composite hydrogel can significantly promote the pulp-dentin complex repair. More importantly, LCS bioceramics-containing composite hydrogel can induce the growth of nerve fibers, leading to the re-innervation of pulp tissues. Taken together, the study suggests that LCS bioceramics can induce the innervation of pulp-dentin complex repair, offering a referable strategy of designing multifunctional filling materials for functional periodontal tissue regeneration.
Dental Pulp/drug effects* ; Hydrogels/pharmacology* ; Animals ; Ceramics/pharmacology* ; Dentin/drug effects* ; Biocompatible Materials/pharmacology* ; Rats ; Gelatin ; Regeneration/drug effects* ; Cell Differentiation/drug effects* ; Injections ; Humans ; Odontogenesis/drug effects*

Objective: To explore the association between mammalian sterile 20-like kinase 2(MST2) gene polymorphism and haplotype and the risk of colorectal cancer, rectal cancer, and colon cancer in the Han population in Baotou area by case-control association study. Methods: A total of 390 patients with colorectal cancer diagnosed by pathology and 413 normal physical examination pop-ulation were collected, and 2 mL of peripheral blood was taken for subsequent gene genotyping. Single nucleotide polymorphisms(SNPs) of MST2 gene were screened according to the genetic polymorphism data of Chinese Han population provided by the NCBI-Hapmap database. Gene genotyping was performed by Taqman method. Logistic regression was used to calculate the association between each SNP and the risk of colorectal cancer, colon cancer, and rectal cancer under codominant, dominant, overdominant, and recessive genetic models. Results: Five SNPs of MST2 gene were screened, namely rs11783149, rs10955176, rs7827435, rs4075986, rs3019295. Among them, SNP rs4075986 was associated with the risk of colorectal cancer. Compared with the rs4075986 GG+AA genotype, carrying the AG genotype [OR(95%CI)=2.473(1.844-3.316) could increase the risk of colorectal cancer. Compared with the rs4075986 GG genotype, carrying the AG+AA genotype [OR(95%CI)=2.475(1.844-3.323) could increase the risk of colorectal cancer. SNP rs4075986 and rs3019295 were associated with the risk of rectal cancer. Compared with the rs4075986 GG+AA genotype, carrying the AG genotype [OR(95%CI)=3.411(2.387-4.874)] could increase the risk of rectal cancer. Compared with the rs3019295 GG+AA genotype, carrying the AG genotype [OR(95%CI)=0.706(0.501-0.996)] could reduce the risk of rectal cancer. SNP rs11783149 and rs4075986 were associated with the risk of colon cancer. Compared with the rs11783149 CC genotype, carrying the TT [OR(95%CI)=10.883(1.186-99.862)] and CT [OR(95%CI)=1.665(1.036-2.675)] genotype could increase the risk of colon cancer, respectively. Compared with the rs4075986 GG genotype, the AG+AA genotype [OR(95%CI)=1.824(1.262-2.638)] could increase the risk of colon cancer. Conclusion MST2 gene SNP rs3019295 AG genotype may be protective factor for rectal cancer. SNP rs11783149 CT and TT genotypes maybe risk factors for colon cancer. SNP rs4075986 AG and AG+AA genotypes may be a common risk factors for colorectal cancer, rectal cancer and colon cancer.

Objective This study aims to evaluate the application of BOPPPS teaching model combined with case and problem-based learning(CPBL)and the scenario simulation in cardiovascular internal medicine education.Methods The study included cardiovascular internal medicine graduates from the 2022 and 2023 cohorts.The 2022 cohort(n=12)served as the control receiving traditional teaching methods,while the 2023 cohort(n=16)was the experimental group,which utilized the BOPPPS model combined with CPBL and scenario simulation.The students theoretical examination scores were assessed and a questionnaire survey was conducted to evaluate self-assessment of abilities and teaching satisfaction among the students in the experimental group.Results The examination scores of experimental group were significantly higher(97.94±3.46)as compared to that of control group(69.13±12.88)(P＜0.05).Over 93.75%of the students in the experimental group strongly or somewhat agreed that the combined teaching model stimulated their learning interest,improved learning efficiency,facilitated their capacity building of autonomous learning,theoretical knowledge,helped establish clinical reasoning,and improved their teamwork skills.Additionally,over 93.75%of the students were highly satisfied with the course design,emphasizing key content,pro-moting teacher-student interaction,and expressed willingness to continue with this teaching method in the future.Conclusions The application of the BOPPPS teaching model combined with CPBL and scenario simulation in cardio-vascular internal medicine education achieved excellent teaching outcomes.It effectively stimulated students interest in learning,enhanced autonomous learning abilities,and received high satisfaction ratings from students.

OBJECTIVE To investigate and analyze the use of acetaminophen in primary medical institutions of Shaanxi province， and to provide evidence for promoting the standardized and rational use of acetaminophen. METHODS According to the method of cluster stratified random sampling， all prescriptions of acetaminophen issued by primary medical institutions in one district and one county （or two districts） were randomly selected from 10 provincial cities of Shaanxi province from 2020 to 2023； the existing clinical diagnoses were classified by using the International Classification of Diseases （ICD） code， and the drug information of collected prescriptions was analyzed descriptively. SPSS 25.0 software was used for single-factor analysis and Logistic regression analysis to find out the key factors affecting the duration of medication ＞10 d. RESULTS A total of 7 375 valid prescriptions for acetaminophen were collected in this study. The patients who used acetaminophen were mainly female （52.11%） and aged 19-64 （66.73%）. Based on the ICD code， the disease categories most involved in the use of acetaminophen were musculoskeletal system， connective tissue diseases or symptoms and signs （43.48%）； the top 3 clinical diagnoses were joint disease （25.59%）， fracture （9.95%）， and toothache （8.58%）. Among the 7 175 prescriptions with clear drug usage and dosage， 3 366 were in line with the recommendation of acetaminophen instruction， and 5.63% of the prescriptions exceeded the maximum dose limit of acetaminophen 2.0 g/d. There were 4 051 prescriptions exceeding the conventional limit of treatment duration （7 d）， and 1 336 prescriptions exceeding the limit of treatment duration （10 d）. The main factors affecting the duration of drug treatment ＞10 d were the region and type of medical institutions， the gender and age of patients， and the phenomenon of the duration of drug treatment ＞10 d was common in the primary medical institutions from southern Shaanxi， township health centers， the elderly and female patients. CONCLUSIONS There are some unreasonable clinical applications of acetaminophen in primary medical institutions of Shaanxi province， which are mainly manifested in inappropriate usage and dosage， unsuitable clinical diagnosis and drug duration. The region， type of medical institution， age and gender of patients will affect the duration of this drug prescription.

Objective:To discuss the effect of royal jelly acid(10-HDA)on the proliferation and migration of the human colon cancer SW620 cells based on the network pharmacology,and to clarify its related molecular mechanism.Methods:The active ingredients such as 10-HDA and their corresponding targets were retrieved by using the keyword"royal jelly"from the Traditiomal Chinese Medicine Systems Pharmacology(TMSCP)Database and the Traditiomal Chinese Medicine Integrated Database(TCMID);the small molecule targets were predicted by the Swiss Target Prediction Database.The GeneCards Database and the Online Mendelian Inheritance in Man(OMIM)Database were used to obtain the targets with the keyword"Colon Cancer";the protein-protein interaction(PPI)network was constructed by using the String Database and Cytoscape 3.8.0 Software to screen the core targets;the Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were analyzed by Metascape Database;the specific ingredient 10-HDA was screened for the in vitro activity experiments.The human colon cancer SW620 cells with good growth status were divided into control group and different doses(1,5,10,15,and 20 mmol·L-1)of 10-HDA groups.The viabilities of the cells in various groups were detected by MTT method and the survival rates of the cells were calculated.The SW620 cells were divided into control group,low dose(5 mmol·L-1)of 10-HDA group,middle dose(10 mmol·L-1)of 10-HDA group,and high dose(15 mmol·L-1)of 10-HDA group;Hoechst33342 staining method was used to observe the morphology of the cells in various groups;cell scratch test was used to detect the scratch healing rates of the cells in various groups;flow cytometry was used to detect the percentages of the cells at different cell cycles in various groups;biochemical method was used to detect the activities of total antioxidant capacity(T-AOC)and superoxide dismutase(SOD)in the cells in various groups;Western blotting method was used to detect the expression levels of B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),cysteine-containing aspartate proteolytic enzyme-3(Caspase-3),cysteine-containing aspartate proteolytic enzyme-9(Caspase-9),glycogen synthase kinase 3β(GSK3β),β-catenin,and cyclin D1 proteins in the cells in various groups.Results:Six active ingredients of royal jelly were screened out by the TCMSP Database,and 28 core targets of 10-HDA in the treatment of colon cancer were obtained.The GO function enrichment analysis mainly included the signaling pathways such as cell proliferation and apoptosis.The KEGG signaling pathway enrichment analysis included the cell cycle,prostate cancer,cell senescence,and p53 signaling pathways;the GSK3β/β-catenin signaling pathway was closely related to the cell cycle.Compared with control group,the viabilities of the cells in 5,10,15,and 20 mmol·L-110-HDA groups were decreased in a dose-dependent manner(P<0.05 or P<0.01),the numbers of apoptotic cells in different doses of 10-HDA groups were significantly increased,and the scratch healing rates of the cells were significantly decreased(P<0.05 or P<0.01);the percentages of the cells at S phase in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),the activities of T-AOC and SOD in the cells in different doses of 10-HDA groups were significantly decreased(P<0.05 or P<0.01).Compared with control group,the expression level of Bcl-2 protein in the cells in low dose of 10-HDA group was significantly decreased(P<0.01),and the expression level of GSK3β protein was significantly increased(P<0.05);compared with control group,the expression levels of Bax,Caspase-3,Caspase-9,and GSK3β proteins in the cells in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),and the expression levels of Bcl-2,β-catenin,and CyclinD1 proteins were significantly decreased(P<0.01).Conclusion:10-HDA can significantly inhibit the proliferation and migration of the colon cancer cells and promote the apoptosis and oxidation levels of the colon cancer cells,and its mechanism may be related to the activation of the GSK3β/β-catenin signaling pathway.

Objective To establish a preliminary evaluation system for gastrointestinal qi stagnation syndrome.Methods On the basis of the systematic evaluation of medical literature in the early stage of the research group,24 high-frequency items were subjected to Delphi method,the item indexes were determined through three rounds of expert consultation,and the proportion value of the indexes was determined by AHP,and the evaluation system of gastrointestinal qi stagnation syndrome was initially constructed.Results A total of 84 valid questionnaires were collected by three rounds of Delphi method,including 15 in the first round,32 in the second round and 37 in the third round.According to the statistics,16 items including distention(stuffy)or distending pain or moving pain(epigastric,abdominal,etc.),belching,borborygmus,flatus,etc.were selected.The order of the proportion of the first level indexes obtained by the analytic hierarchy process from high to low is:clinical symptoms,pulse,tongue;The proportion of secondary indicators from high to low is as follows:distention(stuffy)or distending pain or moving pain(epigastric,abdominal,etc.),pulse string,greasy fur,thin white fur,slippery pulse string,pulse sinking string,light red tongue,flatus,borborygmus,belching,induced or aggravated in case of emotional distress,hiccup,abdominal mass,anorexia,vomiting,belching and swallowing acid.Conclusion Delphi method and analytic hierarchy process have been used to study gastrointestinal qi stagnation syndrome,and an evaluation system has been preliminarily formed.The index structure is reasonable,targeted and has strong clinical practicability.

Objective:To investigate the relationship between glycemic variability and glycosylated hemoglobin (HbA1c) level during follow-up in elderly male patients with type 2 diabetes.Methods:Retrospective cohort study. A total of 200 elderly male patients who received continuous glucose monitoring from January 2007 to January 2011 were recruited in the Second Medical Center of PLA General Hospital. The subjects were divided into two groups according to baseline mean amplitude of glycaemic excursion (MAGE) level, including MAGE <3.9 mmol/L group ( n=114) and MAGE ≥3.9 mmol/L group ( n=86). The correlation between baseline MAGE and mean HbA1c during follow-up were evaluated by univariate Pearson correlation analysis and multivariate linear regression analysis. Results:Baseline characteristics including age, body mass index, waist circumference, smoking, drinking, fasting blood glucose, blood lipid and blood pressure were comparable between MAGE <3.9 mmol/L group and MAGE ≥3.9 mmol/L group. The average follow-up period was 12.5 years. The mean HbA1c during follow-up in MAGE ≥3.9 mmol/L group was significantly higher than that in MAGE <3.9 mmol/L group (7.23%±0.72% vs. 6.91%±0.77%, t=-2.94, P=0.004). The proportion of mean HbA1c <7.0% during follow-up in MAGE ≥3.9 mmol/L group was 44.2% (38/86), which was significantly lower than that in MAGE <3.9 mmol/L group [60.5% (69/114), χ 2=5.26, P=0.022]. In univariate analysis, MAGE at baseline was correlated with the mean HbA1c during follow-up ( r=0.306, P<0.001). Multivariate linear regression analysis suggested that the baseline MAGE remained an independent influential factor of mean HbA1c ( β=0.09, 95% CI: 0.03 to 0.15, P=0.006, R2=0.31) after several confounding factors were adjusted. Conclusions:With the increased glycemic variability at baseline, mean HbA1c level during follow-up is accordingly elevated. The glycemic variability at baseline is independently related to mean HbA1c level during follow-up in elderly male patients with type 2 diabetes.

Objective To describe and compare the attitude and actual participation of decision-making regarding nursing care of patients with breast cancer, and to identify the related factors. Methods To investigate 480 cases of inpatients with breast cancer in 3 Grade ⅢA hospitals in Wuhan through questionnaire and self-designed general information questionnaire. Results There were significant differences (χ2=28.3, P<0.01) between the attitude and actual participation of decision making regarding of nursing care. The results of Logistic regression analysis showed that patients with higher education level (B=1.574, P=0.002), less children (B=-2.716, P<0.01) and higher income (B=0.323, P<0.01) , had a more active attitude to participate decision making; patients who were younger (B=-6.001, P=0.015), with higher education level (B=1.643, P=0.000), shorter duration of disease (B=-2.413, P=0.022), and lower degree of TNM stage (B=0.618, P=0.012), actually participated more often in decision making. Conclusions The actual participation was inconsistent with the attitude of decision-making regarding nursing care among patients with breast cancer. And patients′ demographic characters were related to their participation of decision making, which suggested that nurses should make a comprehensive assessment of willingness and capacity of patients′decision-making participation, identify the facilitators and barriers, and take measures to support patients to take an active part in the decision making to improve the quality of nursing care.

Objective To explore the efficacy and clinical value of texture analysis of conventional MRI image for the preoperative classification of meningiomas. Methods The MR images of 101 meningioma cases were retrospectively analyzed, all of them underwent routine MRI before operation, and confirmed by surgery and pathology,of whom 81 cases in WHO Ⅰ,19 cases in Ⅱand 1 case in Ⅲ.The maximum diameter of the tumor in MRI images was outlined as ROI by the Image J software.The histograms and grey-level co-occurrence matrix(GLCM)were used to measure the texture parameters,such as maximum value,minimum value,standard deviation(SD),skewness,kurtosis,angular second moment,contrast,inverse different moment, entropy, correlation and so on, and compared with postoperative pathological grading results.The independent sample t test or the Mann-Whitney U test was used to compare the difference of the histogram and the gray level co-occurrence matrix parameter of the MRI images between low-grade and high-grade meningiomas. ROC curves for statistically significant parameters were used to confirm their efficacy in predicting the preoperative grade of meningiomas.Results (1)In histogram parameters,the SDs of T2WI,FLAIR,ADC(SDT2WI,SDFLAIR,SDADC)of low grade meningioma were 14.764(10.928,17.932),9.753 (7.385,13.618) and 12.171 (9.138,19.691), the high grade meningiomas were 19.252 (13.580,25.715), 13.568 (8.936,17.108) and 16.636 (13.166,21.498), respectively. The difference between the two groups was statistically significant(Z values were-2.863,-2.250,-2.247,P respectively 0.004,0.024,0.025).The skewness values (SkeADC, SkeFLAIR) of ADC sequence and FLAIR sequence of low-grade meningiomas were 1.377 ± 1.172 and-1.327 ± 0.930, respectively, and the high-grade meningiomas were 2.503 ± 1.613 and-0.827±0.834,respectively.The differences between the two groups were statistically significant (t values were-2.196,-3.129, P values were 0.002,0.030, respectively). (2) In the GLCM parameters, entropy (EntT1WI, EntT2WI, EntFLAIR, EntADC) of the enhanced T1WI, T2WI, FLAIR and ADC sequences of low grade meningiomas were 6.881(6.174,7.305),6.534±0.598,6.019±0.588,6.040±0.588,high-grade meningiomas were 7.079 (6.742,7.739), 7.014 ± 0.514,6.370 ± 0.703,6.576 ± 0.450, respectively. And the difference between the two groups was statistically significant (Z=-2.007, t values were-3.294,-2.327,-3.245, P values were 0.045,0.001,0.022,0.002,respectively).(3)The ROC curves of EntADCand SkeADCwere plotted, and the area under the curve(AUC)was 0.768 and 0.710,respectively.Combined EntADC,SkeADCand EntT2WI were the best for the classification of meningiomas,and AUC was 0.799.Conclusion Texture analysis can provide more quantification information, which can be more accurately distinguishing high grade meningiomas and low grade meningiomas before surgery.