Objective To explore the relationship between education level and the risk of all-cause mortality in the middle-aged and elderly (≥45 years old) population in China. Methods Using data from five surveys from 2011-2020, years of education, age, gender, marital status, type of household, alcohol consumption status, smoking status, physical activity, limited ability to perform activities of daily living (ADLs), chronic disease status, and body mass index were collected. According to the survival status，the study participants were divided into a survival group (n=8625) and an all-cause mortality group (n=1735). Cox proportional risk regression model was used to analyze the relationship between years of education and the risk of all-cause mortality in middle-aged and elderly people with stratified analysis. Results The survey was conducted on 10360 research subjects, including 4 983 males and 5 377 females, with an age M(Q_R) of 59(8) years old. A total of 88 187 person years (average 8.512 person years) were followed up, and a total of 1735 deaths were reported over 9 years. The all-cause mortality rate was 19.674 ‰, with an education period M(Q_R) of 5(8) years and a survival time M(Q_R) of 9 (0) years. After adjusting for confounding factors, for every 1 year increase in education, the risk of all-cause mortality decreased by 2.60% [HR=0.974, 95% CI (0.960-0.988)]. The stratified analysis results showed that in the population aged 45-59, for every 1 year increase in education, the risk of all-cause mortality decreased by 1.00% [HR=0.990, 95% CI (0.959,1.021)]; In the population aged 60-74 and over 75, for every 1 year increase in education, the risk of all-cause mortality decreased by 2.70% [HR=0.973, 95% CI (0.948, 0.999)] and 3.50% [HR=0.965, 95% CI (0.929, 1.003)], respectively. Conclusion Improving the education level of middle-aged and elderly people (≥ 45 years old) in China can reduce the risk of all-cause mortality, and elderly education should be vigorously promoted.

OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

OBJECTIVE To explore comprehensive management and potential issues associated with long-term prescriptions medications of psychiatry， in order to provide a reference for the comprehensive management of long-term prescriptions of psychiatry in psychiatric hospitals and other medical institutions’ pharmacies. METHODS Starting from the applicable principles for long-term prescriptions of psychiatry， this study introduced the standardized assessment and precautions before issuing long-term prescriptions， the formulation and adjustment of the drug list， as well as the rational management of the long-term prescriptions. It also analyzed potential issues that may arise in the comprehensive management of long-term prescription medications and proposed corresponding countermeasures and suggestions. RESULTS & CONCLUSIONS Prior to initiating long-term prescriptions， a standardized assessment should be conducted on patients from the aspects of their psychiatric condition and long-term potential risk factors， pharmacological treatment plans and other non-pharmacological therapies， physical illnesses. Additionally， healthcare providers should fulfill their obligation to inform patients or their family members. The comprehensive management of long-term prescription medications should be jointly established and improved by multiple departments， and the formulation of drug catalogs should avoid including drugs with potential social harm or medication risks while complying with policy requirements. Furthermore， measures such as adding special identifiers to long-term prescriptions， providing patients with reminders about （No.YGLX202537） prescription expiration， or offering online consultations can also effectively enhance the rationality of medication use under long-term prescriptions. Currently， the implementation of long-term prescriptions in psychiatry remains challenged by inconsistencies in prescription duration， incomplete coverage of diagnostic categories， poor patient adherence， and the risk of deviation in clinical assessments. In this regard， measures such as collaborating with multiple departments to strengthen long-term prescription information management， providing matching pharmaceutical services， ensuring the quality and rationality of long-term prescription implementation， and using modern methods to screen high-risk patients can be taken to improve patient medication compliance and safety.

OBJECTIVE To optimize the salt-processing technology for Anemarrhena asphodeloides. METHODS Taking soaking time， stir-frying temperature， and stir-frying time as factors， Box-Behnken response surface methodology was employed to optimize the salt-processing technology of A. asphodeloides using the contents of mangiferin， neomangiferin， isomangiferin， timosaponin BⅡ， timosaponin AⅢ， timosaponin BⅢ， total flavonoids， and total saponins as evaluation indicators. The entropy weight method was applied to determine the weight of each indicator and calculate the comprehensive score. Based on the 17 sets of Box-Behnken response surface methodology results， a genetic algorithm （GA）-back propagation （BP） neural network was used to further optimize the salt-processing technology， with soaking time， stir-frying temperature， and stir-frying time as input layers and the comprehensive score as the output layer. The salt-processing parameters obtained from the two methods were validated and compared to determine the optimal salt-processing technology for A. asphodeloides. RESULTS The optimal salt-processing conditions obtained via the Box-Behnken response surface methodology were as follows： soaking time of 23 min， stir-frying temperature of 160 ℃ ， and stir-frying time of 12 min， yielding a comprehensive score of 63.370 2. The GA-BP neural network optimization resulted in the following conditions： soaking time of 24 min， stir-frying temperature of 163 ℃， and stir-frying time of 12 min， with a comprehensive score of 65.163 8. The GA-BP neural network optimization outperformed the results obtained by Box-Behnken response surface methodology. CONCLUSIONS This study successfully optimized the salt-processing technology for A. asphodeloides. Specifically， the technology involves adding 15 mL of 0.1 g/mL saline solution to 50 g of the herbal slices， allowing them to moisten for 24 minutes， and then stir-frying at 163 ℃ for 12 minutes.

BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

Objective:To explore the pathogenesis and potential biomarkers of atrial fibrillation based on bioinformatics.Methods:Differentially expressed genes and module genes related to atrial fibrillation were obtained from GSE41177 and GSE79768 datasets(Chinese-origin tissue samples)through differential expression analysis and weighted gene co-expression network analysis.Candidate hub genes were obtained by taking intersections,and hub genes were obtained after gender stratification.Subsequently,functional enrichment analysis and immune infiltration analysis were performed.Four machine learning models were constructed based on the hub genes,and the optimal model was selected to construct a prediction nomogram.The prediction ability of the nomogram was verified using calibration curves and decision curves.Finally,potential therapeutic drugs for atrial fibrillation were screened from the DGIdb database.Results:A total of 67 differentially expressed genes and 65 module genes related to atrial fibrillation were identified.Functional enrichment analysis indicated that the pathogenesis of atrial fibrillation was closely related to inflammatory response,immune response,and immune and infectious diseases.Four common hub genes(TYROBP,FCER1G,EVI2B and SOD2),and two genes specifically expressed in male(PILRA and SLC35G3)and female(HLA-DRA and GATP)patients with atrial fibrillation were obtained after gender-segregated screening.The extreme gradient boosting model had satisfactory diagnostic efficiency,and the nomogram constructed based on the hub genes,male significant variables(PILRA,SLC35G3 and SOD2),and female significant variables(FCER1G,SOD2 and TYRO BP)had satisfactory predictive ability.Immune infiltration analysis demonstrated a disturbed immune infiltration microenvironment in atrial fibrillation with a higher abundance of plasma cells,neutrophils,and γδT cells,with a higher abundance of neutrophils in males and resting mast cells in females.Two potential drugs for the treatment of atrial fibrillation,valproic acid and methotrexate,were obtained by database and literature screening.Conclusions:The pathogenesis of atrial fibrillation is closely related to inflammation and immune response,and the microenvironment of immune cell infiltration of cardiomyocytes in the atrial tissue of patients with atrial fibrillation is disordered.TYROBP,FCER1G,EVI2B and SOD2 serve as potential diagnostic biomarkers of atrial fibrillation;PILRA and SLC35G3 serve as potential specific diagnostic biomarkers of atrial fibrillation in the male population,which can effectively predict the risk of atrial fibrillation development and are also potential targets for the treatment of atrial fibrillation.

Objective:To observe the application effect of BOPPPS combined with scenario simulation in standardized training of residents for "ultrasound-guided regional anesthesia" (UGRA).Methods:The anesthesiology students enrolled in 2019 for standardized resident training were selected as research objects. A total of 44 students were randomly divided into observation group ( n=22) and control group ( n=22). The control group received traditional teaching and the observation group received the BOPPPS combined with scenario simulation teaching. The differences in comprehensive theoretical knowledge and comprehensive ability of UGRA between the two groups were analyzed through the final assessment. The satisfaction of the two groups of students with teaching process was analyzed using the teaching feedback questionnaire. SPSS 20.0 statistical software was used for the t-test, and the non-parametric test was used in cases of unequal variance. Results:Compared with the control group, the observation group showed significantly higher scores of comprehensive theoretical knowledge [(75.86±9.31) points vs. (64.00±7.76)points] and ultrasonic image interpretation [(37.73±4.60) points vs. (30.86±4.57) points] ( P<0.05). Compared with the control group, the observation group showed significantly reduced time of ultrasonic localization of target nerve [(92.00±22.67) seconds vs. (107.32±23.35) seconds] and the puncture time of simulated teaching aids [(67.82±17.83) seconds vs. (103.18±19.15) seconds] ( P<0.05). The overall satisfaction of students was significantly higher in the observation group than in the control group ( P<0.05). Conclusions:The teaching method of BOPPPS combined with scenario simulation is helpful to improve students' comprehensive ability of UGRA such as comprehensive theoretical knowledge, the interpretation of ultrasound image, and the localization of target nerve.

Objective To study the distribution of intestinal flora in osteoporosis patients with spleen deficiency syndrome.Methods According to the diagnostic criteria of osteoporosis of the World Health Organization(WHO)and the syndrome differentiation criteria of spleen deficiency syndrome in traditional Chinese medicine(TCM),26 healthy attenders with normal bone mass while without spleen deficiency were selected from the population visited Shunde Hospital of Guangzhou University of Chinese Medicine from January 2022 to September 2023 as the normal bone mass group,23 patients with bone mass reduction and spleen deficiency syndrome served as decreased bone mass with spleen deficiency group(shorten as DBM-SD group),and 69 patients with osteoporosis and spleen deficiency syndrome diagnosis were osteoporosis with spleen deficiency group(shorten as OS-SD group).A total of 118 attenders were enrolled in the analysis.The gender,age,body height,body weight,and body mass index(BMI)of the subjects were collected.The bone mineral density(BMD)and serum levels of calcium and alkaline phosphatase(ALP)of the subjects were measured.Stools were collected for the detection of the sequence of the 16SrRNA V3-V4 region,and the sequencing results were given species annotation,and then the correlation of community difference between groups and BMD with the intestinal flora was explored.Results(1)There were significant differences in the relative abundance of intestinal flora between the normal bone mass group and the OS-SD group:differences were shown in Firmicutes(t=2.490,P=0.016),Verrucomicrobia(t=2.180,P=0.003)and Fusobacteria(t=2.270,P=0.026),in Acidobacteria(t=3.003,P=0.003),Lactobacillus(t=3.150,P=0.002)and Bifidobacterium(t=7.248,P=0.001),and in Fecalibacterium(t=2.810,P=0.006)and Rothia(t=2.810,P=0.006).(2)There were significant differences in the relative abundance of intestinal flora between the normal bone mass group and the DBM-SD group:differences were shown in Lactobacillus(t=3.841,P=0.001)and Bifidobacterium(t=2.712,P=0.01),and in Faecalibacterium(t=2.466,P=0.017).(3)There were significant differences in the relative abundance of intestinal flora between the OS-SD group and DBM-SD group:differences were shown in Firmicutes(t=2.321,P=0.025),Bacteroidetes(t=0.393,P=0.020)and Verrucomicrobia(t=3.109,P=0.031).(4)The results of logistic regression analysis showed that in the OS-SD group,lumbar BMD was negatively correlated with Lactobacillus(R=0.355,P=0.003)and Bifidobacterium(R=0.366,P=0.002),positively correlated with Bacteroides(R=0.245,P=0.042),and was negatively correlated Rothia(R=0.330,P=0.006).Conclusion Some bacteria in the intestinal flora are related to the BMD of osteoporosis patients with spleen deficiency syndrome,and significant difference exists in the distribution of intestinal flora between the normal bone mass group and the OS-SD group.The results will provide a theoretical basis for the prevention and treatment of osteoporosis patients with spleen deficiency syndrome from the perspective of the changes of intestinal flora.