Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n＝3), RA patients without lung involvement (n＝3), and healthy controls (n＝3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.

Objective The aim of this study was to investigate the effect of p38 on stem cell maintenance of pancreatic cancer. Methods Human pancreatic cancer cells PANC-1 were treated with different concentrations of 5-fluorouracil(5-FU)(0.5×IC₅₀, IC₅₀, and 2×IC₅₀) for 24 hours, and VX-702 (p38 phosphorylation inhibitor) was added, and the cells were inoculated in 6-well culture dishes with ultra-low adhesion to observe the changes of sphere tumors. The expression levels of cyclin-dependent kinase 2(CDK2), cyclin B1 and D1, Octamer-binding transcription factor 4(OCT4), SRY-box transcription factor 2(SOX2), Nanog and p38 were measured by Western blot. The mRNA expression levels of p38, OCT4, Nanog and SOX2 were tested by RT-PCR. Cell cycle, apoptosis, and the proportion of CD44⁺CD133⁺PANC-1 cells were evaluated by flow cytometry. Results The results showed that 5-FU inhibited the formation of tumor spheres in PANC-1 cells, increased CD44⁺CD133⁺cell fragments, down-regulated the expression of OCT4, Nanog and SOX2, and inhibited the stemness maintenance of PANC-1 tumor stem cells. Phosphorylation of PANC-1 cells was inhibited by a highly selective p38 MAPK inhibitor, VX-702(p38 mitogen-activated protein kinase inhibitor), which had the same effect as 5-FU treatment. When VX-702 combined with 5-FU was used to treat PANC-1 cells, the therapeutic effect was enhanced. Conclusion p38 inhibitors decreased PANC-1 cell activity and increased cell apoptosis. p38 inhibitors inhibit the stemness maintenance of pancreatic cancer stem cells.
Humans ; Phosphorylation/drug effects* ; Cell Line, Tumor ; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors* ; Neoplastic Stem Cells/metabolism* ; Drug Resistance, Neoplasm/drug effects* ; Fluorouracil/pharmacology* ; Pancreatic Neoplasms/pathology* ; Apoptosis/drug effects* ; SOXB1 Transcription Factors/genetics* ; Octamer Transcription Factor-3/genetics*

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*

Objective To explore the mediating effect of health-promoting lifestyle on the relationship between health literacy and stigma among middle-aged and elderly patients with type 2 diabetes mellitus (T2DM). Methods A stratified random sampling method was used to select 415 patients with T2DM from three general hospitals in Weifang to conduct a questionnaire survey using the Disease Stigma Assessment Scale for Type 2 Diabetes Mellitus (DSAS-2), the Health Literacy Scale, and the Type 2 Diabetes Health Promotion Scale (T2DHPS). Results Sickness stigma was negatively correlated with health literacy (r=-0.547, P<0.01) and negatively correlated with health promotion (r=-0.505, P<0.01), while health promotion was positively correlated with health literacy (r=0.398, P<0.01). Health-promoting lifestyle mediated the association between health literacy and stigma (β=0.0383, P<0.01), with the mediating effect accounting for 16.00% of the total effect. Conclusion Health literacy can influence the stigma of patients with type 2 diabetes mellitus through health promotion lifestyle, suggesting that the stigma of patients with diabetes can be improved through health promotion lifestyle intervention.

Objective It constructs a new culture index system for high-quality development of public hospitals to provide scientific tool for evaluating the level of new culture construction of public hospitals and promoting high-quali-ty development.Methods A pool of indicators was established based on policy combing and literature research.Then,an indicator system was formed through Delphi expert consultation and demonstration,and weighting coefficients were assigned using the hierarchical analysis method.Results The indicator system of the new culture in public hospi-tals contains four primary indicators,eight secondary indicators and 23 specific entries.The four primary indicators are hospital culture system construction,strengthening the orientation of patients'needs,caring for medical staff and distinctive hospital culture.The effectiveness of implementation as an additional dimension contains two secondary indicators and eight specific entries.The weights of the primary indicators are balanced.Among the sec-ondary indicators,institutional planning(0.250),staff care(0.170),medical services(0.130),discipline branding(0.125)and professionalism(0.125)have higher weights.Conclusion The new culture index system for high-quality development of public hospitals is in line with Xi Jinping's cultural thought and the requirements of the new culture for high-quality development of public hospitals.It needs to pay attention to the planning of the cultural system,em-phasises the care of employees and the cultivation of professionalism,and focuses on the construction of medical services and disciplinary brands,so as to promote the construction of the new culture in public hospitals in line with the requirements of the national strategies.

Objective It constructs a new culture index system for high-quality development of public hospitals to provide scientific tool for evaluating the level of new culture construction of public hospitals and promoting high-quali-ty development.Methods A pool of indicators was established based on policy combing and literature research.Then,an indicator system was formed through Delphi expert consultation and demonstration,and weighting coefficients were assigned using the hierarchical analysis method.Results The indicator system of the new culture in public hospi-tals contains four primary indicators,eight secondary indicators and 23 specific entries.The four primary indicators are hospital culture system construction,strengthening the orientation of patients'needs,caring for medical staff and distinctive hospital culture.The effectiveness of implementation as an additional dimension contains two secondary indicators and eight specific entries.The weights of the primary indicators are balanced.Among the sec-ondary indicators,institutional planning(0.250),staff care(0.170),medical services(0.130),discipline branding(0.125)and professionalism(0.125)have higher weights.Conclusion The new culture index system for high-quality development of public hospitals is in line with Xi Jinping's cultural thought and the requirements of the new culture for high-quality development of public hospitals.It needs to pay attention to the planning of the cultural system,em-phasises the care of employees and the cultivation of professionalism,and focuses on the construction of medical services and disciplinary brands,so as to promote the construction of the new culture in public hospitals in line with the requirements of the national strategies.

Objective It constructs a new culture index system for high-quality development of public hospitals to provide scientific tool for evaluating the level of new culture construction of public hospitals and promoting high-quali-ty development.Methods A pool of indicators was established based on policy combing and literature research.Then,an indicator system was formed through Delphi expert consultation and demonstration,and weighting coefficients were assigned using the hierarchical analysis method.Results The indicator system of the new culture in public hospi-tals contains four primary indicators,eight secondary indicators and 23 specific entries.The four primary indicators are hospital culture system construction,strengthening the orientation of patients'needs,caring for medical staff and distinctive hospital culture.The effectiveness of implementation as an additional dimension contains two secondary indicators and eight specific entries.The weights of the primary indicators are balanced.Among the sec-ondary indicators,institutional planning(0.250),staff care(0.170),medical services(0.130),discipline branding(0.125)and professionalism(0.125)have higher weights.Conclusion The new culture index system for high-quality development of public hospitals is in line with Xi Jinping's cultural thought and the requirements of the new culture for high-quality development of public hospitals.It needs to pay attention to the planning of the cultural system,em-phasises the care of employees and the cultivation of professionalism,and focuses on the construction of medical services and disciplinary brands,so as to promote the construction of the new culture in public hospitals in line with the requirements of the national strategies.

Objective It constructs a new culture index system for high-quality development of public hospitals to provide scientific tool for evaluating the level of new culture construction of public hospitals and promoting high-quali-ty development.Methods A pool of indicators was established based on policy combing and literature research.Then,an indicator system was formed through Delphi expert consultation and demonstration,and weighting coefficients were assigned using the hierarchical analysis method.Results The indicator system of the new culture in public hospi-tals contains four primary indicators,eight secondary indicators and 23 specific entries.The four primary indicators are hospital culture system construction,strengthening the orientation of patients'needs,caring for medical staff and distinctive hospital culture.The effectiveness of implementation as an additional dimension contains two secondary indicators and eight specific entries.The weights of the primary indicators are balanced.Among the sec-ondary indicators,institutional planning(0.250),staff care(0.170),medical services(0.130),discipline branding(0.125)and professionalism(0.125)have higher weights.Conclusion The new culture index system for high-quality development of public hospitals is in line with Xi Jinping's cultural thought and the requirements of the new culture for high-quality development of public hospitals.It needs to pay attention to the planning of the cultural system,em-phasises the care of employees and the cultivation of professionalism,and focuses on the construction of medical services and disciplinary brands,so as to promote the construction of the new culture in public hospitals in line with the requirements of the national strategies.

Objective It constructs a new culture index system for high-quality development of public hospitals to provide scientific tool for evaluating the level of new culture construction of public hospitals and promoting high-quali-ty development.Methods A pool of indicators was established based on policy combing and literature research.Then,an indicator system was formed through Delphi expert consultation and demonstration,and weighting coefficients were assigned using the hierarchical analysis method.Results The indicator system of the new culture in public hospi-tals contains four primary indicators,eight secondary indicators and 23 specific entries.The four primary indicators are hospital culture system construction,strengthening the orientation of patients'needs,caring for medical staff and distinctive hospital culture.The effectiveness of implementation as an additional dimension contains two secondary indicators and eight specific entries.The weights of the primary indicators are balanced.Among the sec-ondary indicators,institutional planning(0.250),staff care(0.170),medical services(0.130),discipline branding(0.125)and professionalism(0.125)have higher weights.Conclusion The new culture index system for high-quality development of public hospitals is in line with Xi Jinping's cultural thought and the requirements of the new culture for high-quality development of public hospitals.It needs to pay attention to the planning of the cultural system,em-phasises the care of employees and the cultivation of professionalism,and focuses on the construction of medical services and disciplinary brands,so as to promote the construction of the new culture in public hospitals in line with the requirements of the national strategies.

Objective It constructs a new culture index system for high-quality development of public hospitals to provide scientific tool for evaluating the level of new culture construction of public hospitals and promoting high-quali-ty development.Methods A pool of indicators was established based on policy combing and literature research.Then,an indicator system was formed through Delphi expert consultation and demonstration,and weighting coefficients were assigned using the hierarchical analysis method.Results The indicator system of the new culture in public hospi-tals contains four primary indicators,eight secondary indicators and 23 specific entries.The four primary indicators are hospital culture system construction,strengthening the orientation of patients'needs,caring for medical staff and distinctive hospital culture.The effectiveness of implementation as an additional dimension contains two secondary indicators and eight specific entries.The weights of the primary indicators are balanced.Among the sec-ondary indicators,institutional planning(0.250),staff care(0.170),medical services(0.130),discipline branding(0.125)and professionalism(0.125)have higher weights.Conclusion The new culture index system for high-quality development of public hospitals is in line with Xi Jinping's cultural thought and the requirements of the new culture for high-quality development of public hospitals.It needs to pay attention to the planning of the cultural system,em-phasises the care of employees and the cultivation of professionalism,and focuses on the construction of medical services and disciplinary brands,so as to promote the construction of the new culture in public hospitals in line with the requirements of the national strategies.