OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

OBJECTIVE: To establish and validate a novel diabetic retinopathy (DR) risk-prediction model using a whole-exome sequencing (WES)-based machine learning (ML) method. METHODS: WES was performed to identify potential single nucleotide polymorphism (SNP) or mutation sites in a DR pedigree comprising 10 members. A prediction model was established and validated in a cohort of 420 type 2 diabetic patients based on both genetic and demographic features. The contribution of each feature was assessed using Shapley Additive explanation analysis. The efficacies of the models with and without SNP were compared. RESULTS: WES revealed that seven SNPs/mutations ( rs116911833 in TRIM7, 1997T>C in LRBA, 1643T>C in PRMT10, rs117858678 in C9orf152, rs201922794 in CLDN25, rs146694895 in SH3GLB2, and rs201407189 in FANCC) were associated with DR. Notably, the model including rs146694895 and rs201407189 achieved better performance in predicting DR (accuracy: 80.2%; sensitivity: 83.3%; specificity: 76.7%; area under the receiver operating characteristic curve [AUC]: 80.0%) than the model without these SNPs (accuracy: 79.4%; sensitivity: 80.3%; specificity: 78.3%; AUC: 79.3%). CONCLUSION Novel SNP sites associated with DR were identified in the DR pedigree. Inclusion of rs146694895 and rs201407189 significantly enhanced the performance of the ML-based DR prediction model.
Diabetic Retinopathy/diagnosis* ; Humans ; Machine Learning ; Male ; Female ; Polymorphism, Single Nucleotide ; Middle Aged ; Exome Sequencing ; Aged ; Adult ; Pedigree ; Diabetes Mellitus, Type 2/complications* ; Genetic Predisposition to Disease ; Mutation

Breast cancer(BRCA)remains one of the leading causes of cancer-related deaths worldwide due to its high rates of metastasis and recurrence,making it crucial to explore its underlying molecular mechanisms.Our previous study demonstrated that miR-326 inhibits BRCA progression by targeting EPH receptor B3(EPHB3).This study further explores the molecular mechanism by which long non-coding RNAs(LncRNAs)regulates BRCA progression via the competing endogenous RNA(ceRNA)mecha-nism,in which it competes with EPHB3 for miR-326 binding.Bioinformatics analysis identified LncRNA Small Nucleolar RNA Host Gene 12(SNHG12)as a potential miR-326-binding molecule.SNHG12 was found to be significantly upregulated in BRCA tissues,exhibiting a negative correlation trend with miR-326 and a positive correlation trend with EPHB3,suggesting its potential involvement in the ceRNA regu-latory network.Nuclear-cytoplasmic fractionation assays revealed cytoplasmic localization of SNHG12,while dual-luciferase reporter assays confirmed its direct binding to miR-326.Functional experiments demonstrated that SNHG12 knockdown significantly suppressed BRCA cell proliferation,invasion,and migration,while miR-326 inhibition reversed these effects.Furthermore,miRNA pulldown assay re-vealed significant enrichment of SNHG12 and EPHB3 in the miR-326 pulldown products,indicating di-rect binding between them.Western blotting and rescue experiments revealed that SNHG12 upregulates EPHB3 expression by sponging miR-326,thereby promoting the malignant behaviors of BRCA cells.Col-lectively,this study revealed that LncRNA SNHG12 promotes BRCA progression by regulating the miR-326/EPHB3 axis through a ceRNA mechanism.The SNHG12/miR-326/EPHB3 pathway may represent a promising target for the molecular diagnosis and targeted therapy of BRCA.

Objective To investigate the effect of miR-185-5p-mediated targeted negative regulation of transmembrane 9 superfamily member 1(TM9SF1)on proliferation,migration and autophagy in lung adenocarcinoma cells.Methods The expression of miR-185-5p in lung adenocarcinoma tissues was analyzed using dataset GSE51853 downloaded from the Gene Expression Omnibus(GEO)database.Potential target proteins of miR-185-5p were predicted using online databases(miRTargetLink,miRTarbase,and DIANA-microT-CD),and autophagy-related proteins were obtained from HADb.The intersected results from these four databases was identified,and survival curves of vascular endothelial growth factor A(VEGFA)and TM9SF1 within the overlapping candidates were analyzed using the StarBase database.TM9SF1 3'UTR wild-type(WT)or TM9SF1 3'UTR mutant(MUT)reporter plasmids were separately co-transfected with miR-185-5p control plasmid(CON)or miR-185-5p overexpression plasmid(over-miR-185-5p)into HEK-293T cells.A dual-luciferase reporter gene assay was employed to assess the binding interaction between miR-185-5p and TM9SF1 and quantify the subsequent luciferase activity.Western blotting was used to assess TM9SF1 protein expression levels in A549 cells transfected with over-miR-185-5p.A549 cells were divided into three groups:(1)CON+NC group,co-transfected with miR-185-5p control plasmid and TM9SF1 control plasmid;(2)over-miR-185-5p+NC group,co-transfected with over-miR-185-5p and TM9SF1 control plasmid;(3)over-miR-185-5p+over-TM9SF1 group,co-transfected with both miR-185-5p and TM9SF1 overexpression plasmids.EdU cell proliferation assay,wound healing assay,and Transwell migration assay were performed to validate the effects of miR-185-5p targeted binding to TM9SF1 on proliferation and migration capacities in lung adenocarcinoma.Changes in autophagic flux and mitochondrial membrane potential(MMP)of lung adenocarcinoma cells were detected using stubRFP-sensGFP-LC3 lentivirus and JC-1 assays,respectively.Results In the GSE51853 dataset,miR-185-5p expression level was significantly lower in lung adenocarcinoma tissues compared with normal lung tissues(P<0.01).qRT-PCR analysis revealed that miR-185-5p expression was downregulated in lung adenocarcinoma cell lines NCI-H1299 and A549 compared with normal lung epithelial cells BEAS-2B(P<0.01).Bioinformatics predictions using miRTargetLink,miRTarbase,DIANA-microT-CD,and HADb databases indicated that miR-185-5p could target and regulate the autophagy-related protein TM9SF1.Dual-luciferase reporter assays and Western blotting demonstrated that miR-185-5p directly bound to the 3'UTR region of TM9SF1 mRNA,and overexpression of miR-185-5p significantly reduced the expression of target protein TM9SF1(P<0.05).EdU cell proliferation,wound healing,and Transwell migration assays demonstrated that miR-185-5p overexpression inhibited proliferation and migration capacities of lung adenocarcinoma cells,whereas TM9SF1 overexpression could attenuate this inhibition effect(P<0.05).Results of stubRFP-sensGFP-LC3 for autophagic flux analysis demonstrated that overexpression of miR-185-5p enhanced autophagic flux in A549 cells,whereas co-overexpression of miR-185-5p and TM9SF1 suppressed autophagic flux.JC-1 assays showed a decreased MMP level in A549 cells after miR-185-5p overexpression,with higher MMP level observed when miR-185-5p and TM9SF1 were co-overexpressed.Conclusion miR-185-5p may suppress proliferation,migration,and autophagy capacities in lung adenocarcinoma cells by targeting TM9SF1 through negative regulation.

Breast cancer(BRCA)remains one of the leading causes of cancer-related deaths worldwide due to its high rates of metastasis and recurrence,making it crucial to explore its underlying molecular mechanisms.Our previous study demonstrated that miR-326 inhibits BRCA progression by targeting EPH receptor B3(EPHB3).This study further explores the molecular mechanism by which long non-coding RNAs(LncRNAs)regulates BRCA progression via the competing endogenous RNA(ceRNA)mecha-nism,in which it competes with EPHB3 for miR-326 binding.Bioinformatics analysis identified LncRNA Small Nucleolar RNA Host Gene 12(SNHG12)as a potential miR-326-binding molecule.SNHG12 was found to be significantly upregulated in BRCA tissues,exhibiting a negative correlation trend with miR-326 and a positive correlation trend with EPHB3,suggesting its potential involvement in the ceRNA regu-latory network.Nuclear-cytoplasmic fractionation assays revealed cytoplasmic localization of SNHG12,while dual-luciferase reporter assays confirmed its direct binding to miR-326.Functional experiments demonstrated that SNHG12 knockdown significantly suppressed BRCA cell proliferation,invasion,and migration,while miR-326 inhibition reversed these effects.Furthermore,miRNA pulldown assay re-vealed significant enrichment of SNHG12 and EPHB3 in the miR-326 pulldown products,indicating di-rect binding between them.Western blotting and rescue experiments revealed that SNHG12 upregulates EPHB3 expression by sponging miR-326,thereby promoting the malignant behaviors of BRCA cells.Col-lectively,this study revealed that LncRNA SNHG12 promotes BRCA progression by regulating the miR-326/EPHB3 axis through a ceRNA mechanism.The SNHG12/miR-326/EPHB3 pathway may represent a promising target for the molecular diagnosis and targeted therapy of BRCA.

Construct Validity and Reliability of the Malay Version of Rosenberg Self Esteem Scale (RSES) among youth in Southern Malaysia: A Confirmatory Factor Analysis IntroductionThe Rosenberg Self-Esteem Scale (RSES) is widely used to measure self-esteem among adults and youth. This study aims to determine the construct validity and reliability of the Rosenberg Self-Esteem Scale Malay version (RSES-M) among Malaysian youth using Confirmatory Factor Analysis (CFA).MethodologyWe administered the Malay-language RSES to 378 Form Four students in the Kota Tinggi District, selected through multistage sampling. The construct validity of RSES-M was assessed using confirmatory factor analysis (CFA), while internal consistency was measured using Cronbach alpha. AMOS version 26 and SPSS version 20 were used for statistical analysis. We compared three measurement models of the RSES-M for the best relative fit: one uni-dimensional model and two different two-domain models (with different items assigned to each domain for each model).ResultsThe findings indicate that the best model for the RSES-M was a two-domain model, with domain one representing positive self-esteem and domain two representing negative self-esteem. The item “I wish I could respect myself more” demonstrated a strong fit within the CFA model when included under the positive domain of self-esteem (Model 3) compared to negative domain ((Model 2) (Chi-Square/degree of freedom (df) = 3.341, goodness of fit (GFI) = 0.967, Comparative Fit Index (CFI) = 0.905, Incremental Fit Index (IFI) = 0.906, and the Root Mean Squared Error of Approximation (RMSEA) = 0.079 and substantial reliability (Cronbach's alpha for domain one = 0.765, and domain two = 0.648). This finding diverges from the original RSES developed by Morris Rosenberg in 1965, which conceptualised the RSES as a unidimensional construct, and other studies that categorised the item "I wish I could respect myself more" under the negative self-esteem domain.

Thoracic ossification of the ligamentum flavum (TOLF) is a pathological heterotopic ossification disease in which the fibrous tissue of the ligamentum flavum of the thoracic spine converts into bony tissue, often leading to thoracic spinal stenosis and compression of the thoracic spinal cord nerve. When TOLF patients present with symptoms of spinal cord nerve compression, surgical treatment is usually required, and traditional open surgery is more invasive and carries a higher risk of spinal cord nerve injury. In recent years, domestic and foreign researchers have tried to apply spinal endoscopic techniques such as microendoscopy, percutaneous foraminoscopy, and unilateral biportal endoscopy for the treatment of TOLF, which can maximize the preservation of normal bone while achieving adequate decompression of the spinal cord nerve, with less damage to spinal stability, and have the advantages of less surgical trauma, less bleeding, and faster postoperative recovery. Due to the special anatomical structure of the thoracic vertebra, spinal endoscopic techniques should focus on safety and it is recommended that they are performed in experienced centers, and surgical indications should be strictly controlled.

Thoracic ossification of the ligamentum flavum (TOLF) is a pathological heterotopic ossification disease in which the fibrous tissue of the ligamentum flavum of the thoracic spine converts into bony tissue, often leading to thoracic spinal stenosis and compression of the thoracic spinal cord nerve. When TOLF patients present with symptoms of spinal cord nerve compression, surgical treatment is usually required, and traditional open surgery is more invasive and carries a higher risk of spinal cord nerve injury. In recent years, domestic and foreign researchers have tried to apply spinal endoscopic techniques such as microendoscopy, percutaneous foraminoscopy, and unilateral biportal endoscopy for the treatment of TOLF, which can maximize the preservation of normal bone while achieving adequate decompression of the spinal cord nerve, with less damage to spinal stability, and have the advantages of less surgical trauma, less bleeding, and faster postoperative recovery. Due to the special anatomical structure of the thoracic vertebra, spinal endoscopic techniques should focus on safety and it is recommended that they are performed in experienced centers, and surgical indications should be strictly controlled.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.