BACKGROUND: Abnormalities of the switch/sucrose nonfermentable (SWI/SNF) chromatin-remodeling complex are closely related to various cancers, and ARID1B (AT-rich interaction domain 1B) is one of the core subunits of the SWI/SNF complex. Mutations or copy number deletions of the ARID1B gene are associated with impaired DNA damage response and altered chromatin accessibility. However, whether ARID1B deficiency affects the proliferation, migration and invasion abilities of non-small cell lung cancer (NSCLC) cells and its molecular mechanisms remain poorly understood. This study aims to reveal the regulatory role of ARID1B gene deletion on the malignant phenotype of NSCLC cells and its molecular mechanism. METHODS: Online databases were used to analyze the relationship between ARID1B and the prognosis of patients with lung cancer, and the expression levels of ARID1B in lung cancer tissues. The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeat) technology was employed to construct stable ARID1B gene knockout (KO) cell lines. The plate colony formation assay was used to detect cell proliferation, and the Transwell cell migration and invasion assays were used to detect changes in cell migration ability. RNA-Seq was utilized for the expression and enrichment analysis of differentially expressed genes. Western blot (WB) was used to verify the knockout effect of the ARID1B gene and to detect the expression changes of epithelial-mesenchymal transition (EMT) markers and mitogen-activated protein kinases (MAPK) signaling pathway-related proteins. Nude mouse tumor models were constructed and the tumorigenic abilities of control and ARID1B-deficient cells were compared. RESULTS: Patients with low ARID1B expression have poor overall survival. ARID1B is differentially expressed in lung cancer and normal tissues, and its expression level being lower in cancer cells. ARID1B-deficient cells had significantly enhanced in vitro proliferation, migration and invasion abilities. In animal experiments, the tumor formation speed of ARID1B gene deficient cells was significantly accelerated. Enrichment analysis of RNA-Seq results revealed that the differentially expressed genes were mainly enriched in MAPK, phosphoinositide 3-kinase-protein kinase B (PI3K/Akt) and other signaling pathways. WB experiments demonstrated that the expressions of E-cadherin, N-cadherin and Vimentin changed in ARID1B gene deficient cells, and the expressions of MAPK and p-MAPK was increased. CONCLUSIONS The A549-ARID1B KO and PC9-ARID1B KO cell lines were successfully established. The ARID1B-deficient cell lines demonstrated high migration, invasion and proliferation potential at both in vitro and in vivo biological behavior levels and at the transcriptome sequencing level. The changes in the expression of EMT markers and the activation of the MAPK signaling pathway suggest possible metastasis mechanisms of ARID1B-deficient NSCLC.
Humans ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Lung Neoplasms/metabolism* ; Animals ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Transcription Factors/metabolism* ; Neoplasm Invasiveness ; Mice ; DNA-Binding Proteins/metabolism* ; Gene Deletion ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Mice, Nude ; Gene Expression Regulation, Neoplastic

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 latent classes of recurrence fear in nasopharyngeal carcinoma patients and analyze their influencing factors.Methods:From July 2021 to December 2023, convenience sampling was used to select nasopharyngeal carcinoma patients admitted to the Eye and ENT Hospital of Fudan University as research subjects. The survey was conducted using the General Information Questionnaire, Fear of Progression Questionnaire-Short Form, Brief Illness Perception Questionnaire, and Medical Coping Modes Questionnaire. Mplus 8.3 software was used for latent profile analysis. Multivariate logistic regression was used to analyze the factors influencing the different classes of recurrence fear in nasopharyngeal carcinoma patients.Results:A total of 208 questionnaires were distributed, and 208 valid questionnaires were collected, with a valid response rate of 100.00%. The recurrence fear score of 208 nasopharyngeal carcinoma patients was (34.01±8.32). The fear of recurrence in nasopharyngeal carcinoma patients included three latent classes: low fear (19.71%, 41/208), moderate fear (66.83%, 139/208), and high fear (13.46%, 28/208). There were statistically significant differences in gender, working condition, individual monthly income, tumor clinical stage, illness perception, and medical coping modes among nasopharyngeal carcinoma patients with different recurrence fear classes ( P<0.05) . Conclusions:Nasopharyngeal carcinoma patients generally have a fear of recurrence. Medical and nursing staff should focus on patients who are female, retired or unemployed, have low personal economic income, have high tumor stages, have severe negative illness perception, and have negative coping modes, and take effective intervention measures as soon as possible.

Irreparable rotator cuff tear (IRCT) is highly prevalent among the middle-aged and elderly populations, significantly affecting patients' daily lives and functional capabilities. These tears often result from chronic wear and tear, degenerative changes, or acute trauma. Tendon degeneration and scarring make conventional repair surgeries, such as arthroscopic rotator cuff repair, tendon transfer procedures, subacromial bursectomy, and superior capsule reconstruction, yield inconsistent clinical outcomes. Reverse total shoulder arthroplasty (RTSA) reverses the anatomical structure of the glenohumeral joint, medially displaces the humeral head's center of rotation, and distally extends the humeral shaft. This configuration increases the deltoid moment arm during abduction, enhancing glenohumeral joint stability and range of motion. For patients with shoulder joint dysfunction caused by a disrupted force couple balance, this surgical approach can effectively harness the deltoid muscle's power, significantly improving shoulder joint function in the presence of massive rotator cuff defects. The center of rotation of the glenoid prosthesis and the inclination angle of the humeral prosthesis are key factors affecting the prosthesis's stability. RTSA serves not only as a primary treatment option for elderly patients with IRCT but also as a salvage measure after the failure of other treatment plans, demonstrating satisfactory outcomes in the mid to long term. The success rate of surgery and patient satisfaction are influenced by multiple factors. Postoperatively, it is crucial to focus on phased rehabilitation goals and methods following RTSA to ensure that patients can engage in daily activities without exerting undue stress or causing injury to the prosthetic joint. Additionally, potential complications after RTSA, such as glenoid notching, shoulder instability, periprosthetic fractures, and prosthetic joint infection, must be prevented through meticulous preoperative planning, intraoperative techniques, and postoperative management. Should these complications arise, they require timely identification and appropriate treatment. Finally, the contentious issues regarding the use of RTSA in treating IRCT-such as the combination of tendon transfer to improve external rotation, repair of the subscapularis to enhance internal rotation strength, and the indications for surgical age-necessitate further clinical research and long-term follow-up for resolution. These conclusions provide evidence-based guidance for treating patients with IRCT, clarify the advantages and considerations of RTSA in treating IRCT, and aim to offer new perspectives for optimizing treatment plans, improving patient quality of life, and promoting medical research.

Background In the context of improving urban environment for healthy aging, it is necessary to rationally plan and provide community living space and public service facilities suitable for the elderly, and constantly optimize the built environment towards an age-friendly city. Objective To understand the relationship between community built environment and obesity in the elderly in Longgang City, and to provide a reference basis for improving the health of the elderly. Methods Elderly adults aged 60-90 years (n=6527) who completed a physical examination during the period from October 2020 to January 2021 in Longgang City were surveyed, and data on height and weight, waist circumference (WC), and other sociological demographic characteristics were obtained. Overweight was determined by 24 kg·m⁻² ≤ body mass index (BMI) < 28 kg·m⁻² and obesity by BMI ≥ 28 kg·m⁻². Men with WC ≥ 85 cm and women with WC ≥ 80 cm were considered central obesity. Based on the participants' residential addresses, geocoding was performed using a geographic information system, and built environment indicators such as restaurants, convenience stores, and basic medical facilities were obtained using Gaode Map. A binary logistic regression model with adjusted individual-level covariates was used to evaluate the relationship between obesity and built environment indicators among elderly adults by gender and age. Results Among the 6527 community elderly, 46.93% were male and 53.07% were female, with a mean age of (73.69±0.07) years, a mean BMI of (24.32±2.84) kg·m⁻², and 51.92% of the elderly were overweight or obese. The regression results showed that for elderly men, the more convenience stores and the higher mixed land use in residential areas, the higher risk of central obesity; however, the increases in street connectivity and accessibility to parks and recreational areas were associated a decreased risk of central obesity. The prevalence of overweight/obesity was higher among elderly women with more convenience stores in residential areas, while increased street connectivity was associated with a lower prevalence of central obesity among elderly women. Accessibility to primary health care facilities was negatively associated with the risk of central obesity among the 60- to 70-year-olds. For elderly residents aged 71−80 years, higher mixed land use and better accessibility to transit stations were associated with a higher prevalence of overweight/obesity, while street connectivity was negatively associated with the central obesity. Proximity to parks and recreational areas was associated with a reduced risk of overweight/obesity among the 81- to 90-year-olds. Conclusion Among the variables of a 500-m neighborhood built environment, the number of convenience stores, mixed land use, street connectivity, accessibility to primary health care facilities, accessibility to public transit stations, and accessibility to parks and recreational areas are correlated with obesity among elderly residents, and the degree of influence varies by gender and age.

BACKGROUND: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. METHODS: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. RESULTS: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. CONCLUSIONS This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Liver Neoplasms/genetics*

To investigate the enzyme properties of the black sesame polyphenol oxidase (BsPPO), a synthesized Bsppo gene was cloned into the vector pMAL-c5x and expressed in E. coli. Subsequently, the MBP fusion label in the recombinant protein was removed by protease digestion after affinity purification. The synthesized Bsppo gene contained 1 752 bp which encodes 585 amino acids with a deduced molecular weight of 65.3 kDa. Transformation of the recombinant vector into E. coli BL21(DE3) resulted in soluble expression of the fusion protein MBP-BsPPO. The enzymatic properties of the recombinant BsPPO was investigated after MBP fusion tag excision followed by affinity purification. The results demonstrated that the optimal temperature and pH for BsPPO was 25°C and 4.0, respectively. BsPPO exhibited a good stability under low temperature and acidic environment. Low-intensity short-term light exposure increased the activity of BsPPO. Cu²⁺ could improve the activity of BsPPO while Zn²⁺ and Ca²⁺ showed the opposite effect. BsPPO could catalyze the oxidation of monophenols, diphenols, and triphenols, and exhibited good catalytic activity on l-tyrosine and vanillic acid. Moreover, BsPPO exhibited high catalytic activity on black sesame metabolites, including 2-methoxy cinnamic acid, indole-3-carboxylic acid and phloretin. These results may serve as a basis for further characterization of BsPPO.
Catechol Oxidase/genetics* ; Cloning, Molecular ; Escherichia coli/metabolism* ; Recombinant Proteins/genetics* ; Sesamum/genetics*

Background and objective Uridine-diphosphoglucuronosyl transferase 1A1 (UGT1A1),UGT1A1 *28 polymorphism can reduce UGT1A1 enzymatic activity,which may lead to severe toxicities in patients who receive irinotecan.This study tries to build a fragment analysis method to detect UGT1A1 *28 polymorphism.Methods A total of 286 blood specimens from the lung cancer patients who were hospitalized in Guangdong General Hospital between April 2014 to May 2015 were detected UGT1A1*28 polymorphism by fragment analysis method.Results Comparing with Sanger sequencing,precision and accuracy of the fragment analysis method were 100％.Of the 286 patients,236 (82.5％ harbored TA6/6 genotype,48 (16.8％) TA 6/7 genotype and 2 (0.7％) TA7/7 genotype.Conclusion Our data suggest hat the fragment analysis method is robust for detecting UGT1A1 *28 polymorphism in clinical practice.It's simple,time-saving,and easy-to-carry.

Objective To analyze the clinic pathologic factors and survival rate by performing a retro-spective study on the early gastric carcinoma (EGC)with signet ring cell underwent curative gastrostomy (SRC) percentage less than 50%after operation .Methods A total of 424 patients was diagnosed as EGC from January 2008 to January 2010 in Changhai Hospital .The patients were divided into three groups according to the different percentage of SRC within tumor cells , SRC group ( with percentage of SCR more than 50%) , Mixed SRC group (with percentage of SRC less than 50%),and Non-SRC group(Classic adenocarcinoma without SRC ).Then we evaluated the clinic pathologic indicators and prognoses , and study on the relationship with histologic types . Results In ECG,the mixed-SRC group was similar to the SRC group on the phases of onset age and sex .On the other phases,the mixed-SRC group was more associated with mucosa -confined,lower lymph node metasta-sis(LNM),and 5-year survival rate was better than adenocarcinoma group (P<0.05).However,the mixed-SRC group showed more submucosal invasion ,and higher LNM than other groups ( P<0 .05 ) .The mixed-SRC component was one of the independent risk factors of LNM .Conclusion In EGC,mixed-SRC had a more favor-able risk factor of LNM ,showed more aggressive behavior than other groups and displayed poor prognosis .

Carcinoma, Non-Small-Cell Lung ; classification ; therapy ; China ; Humans ; Lung Neoplasms ; classification ; therapy ; Practice Guidelines as Topic ; Receptor Protein-Tyrosine Kinases ; metabolism