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

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.

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.

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:To explore the efficacy of adjuvant chemotherapy and adjuvant immunotherapy combined chemotherapy after radical cystectomy for muscle-invasive bladder cancer (MIBC) with high recurrence risk (pT 2 with positive lymph nodes, and pT 3-4a with or without positive lymph nodes). Methods:A retrospective analysis was conducted on clinical data of 217 patients with bladder cancer admitted to Tianjin Medical University Second Hospital from August 2016 to January 2022. Among them, 183 were male (84.3%) and 34 were female (15.7%), with an average age of (67.3±8.6) years old. All 217 patients underwent radical cystectomy with pelvic lymph node dissection. Based on postoperative adjuvant treatment, the patients were divided into an observation group (147 cases, 67.7%) and a treatment group (70 cases, 32.3%). The observation group and treatment group had similar demographic and pathological characteristics. The age of the observation group and treatment group was (67.4±9.0) years and (66.3±7.6) years, respectively ( P=0.14). The postoperative pathological stages T 2 with lymph node positivity were observed in 8 cases (5.4%) in the observation group and 6 cases (8.6%) in the treatment group. For stages T 3-4awith lymph node positivity, there were 34 cases (23.1%) in the observation group and 18 cases (25.7%) in the treatment group. And there were 105 cases (71.5%) in the observation group and 46 cases (65.7%) in the treatment group of stages T 3-4a without lymph node positivity, respectively( P>0.05). Tumor diameter ≥3 cm was found in 118 cases (80.3%) in the observation group and 54 cases (77.1%) in the treatment group ( P>0.05), while tumor diameter <3 cm was observed in 29 cases (19.7%) in the observation group and 16 cases (22.9%) in the treatment group ( P>0.05).In the treatment group, 36 patients (16.6%) received postoperative chemotherapy with gemcitabine (1 000 mg/m 2, days 1 and 8) and cisplatin (75 mg/m 2, days 2 to 4) (chemotherapy group), while 34 patients (15.7%) received postoperative immunotherapy with checkpoint inhibitors (intravenous infusion of sintilimab 200 mg, terlizumab 200 mg, or toripalimab 240 mg on day 1) in combination with albumin-bound paclitaxel (200 mg on day 2)(immunotherapy combined chemotherapy group). The age of the chemotherapy group and immunotherapy combined chemotherapy group was (66.8±8.4) years and (65.8±6.8) years, respectively ( P>0.05). Postoperative pathological stages T 2 with lymph node positivity were observed in 3 cases (8.3%) in the chemotherapy group and 3 cases (8.8%) in the immunotherapy combined chemotherapy group ( P>0.05). For stages T 3-4awith lymph node positivity, there were 6 cases (16.7%) in the chemotherapy group and 12 cases (35.3%) in the immunotherapy combined chemotherapy group. And there were 27 cases (75.0%) in the observation group and 19 cases (55.9%) in the treatment group of stages T 3-4a without lymph node positivity, respectively( P>0.05). Lymph node involvement was seen in 9 cases (25.0%) in the chemotherapy group and 15 cases (44.1%) in the immunotherapy combined chemotherapy group ( P>0.05). Tumor diameter ≥3 cm was found in 30 cases (83.3%) in the chemotherapy group and 10 cases (29.4%) in the immunotherapy combined chemotherapy group ( P>0.05), while tumor diameter <3 cm was observed in 6 cases (16.7%) in the chemotherapy group and 24 cases (70.6%) in the immunotherapy combined chemotherapy group ( P>0.05). Kaplan-Meier method and multivariate Cox regression test were used to analyze the overall survival (OS) at 1 and 3 years in the observation group and treatment group, as well as the disease-free survival (DFS) at 1 and 3 years in the chemotherapy group and immunotherapy combined chemotherapy group. Additionally, common adverse events were evaluated and compared between the chemotherapy group and immunotherapy combined chemotherapy group based on the criteria published by the U. S. Department of Health and Human Services. Results:The median follow-up time in this study was 18.4 (8.2, 34.7) months. The median follow-up time in the observation group and treatment group was 19.0 (8.3, 35.2) months and 17.5 (7.9, 33.2) months, respectively. The 1-year survival rate was significantly higher in the treatment group compared to the observation group (90.0% vs. 76.2%, χ2=6.92, P=0.009). Similarly, the 3-year survival rate was significantly higher in the treatment group compared to the observation group (82.9% vs. 57.8%, χ2=13.22, P<0.01). The median OS was 35.9 months in the observation group and was not reached in the treatment group, with a statistically significant difference ( HR=2.51, 95% CI 1.36-4.65, P=0.003).In the chemotherapy group and immunotherapy combined chemotherapy group, the median follow-up time was 10.7 (7.4, 22.1) months and 14.4 (6.3, 40.7) months, respectively. The 1-year disease-free survival rate was significantly higher in the immunotherapy combined chemotherapy group compared to the chemotherapy group (91.2% vs. 67.6%, χ2=4.60, P=0.032). The 3-year disease-free survival rate was significantly higher in the chemotherapy group compared to the immunotherapy combined chemotherapy group (88.2% vs. 55.6%, χ2=8.37, P=0.004). The median DFS was 27.7 months in the chemotherapy group and was not reached in the immunotherapy combined chemotherapy group, with a statistically significant difference ( HR=3.39, 95% CI 1.46-7.89, P=0.016).The treatment group had complications classified as follows: 140 cases of grade 1, 39 cases of grade 2, 8 cases of grade 3, 2 cases of grade 4, and 0 case of grade 5 adverse reactions. In the chemotherapy group and the immunotherapy combined chemotherapy group, there were both 5 cases with adverse reactions of grade 3 or higher. Specifically, in the chemotherapy group, there were 2 cases of anemia, 2 cases of decreased platelet count, and 1 case of decreased neutrophil count. In the immunotherapy combined chemotherapy group, there was 1 case of anemia, 1 case of decreased platelet count, and 2 cases of decreased neutrophil count. Additionally, there was 1 case with elevated gamma-glutamyltransferase (γ-GT) in the immunotherapy combined chemotherapy group. The incidence of adverse events of grade 3 or higher in the chemotherapy group and immunotherapy combined chemotherapy group was 13.9% and 14.7%, respectively, with no statistically significant difference( χ2=0.01, P=0.922). Conclusions:Adjuvant therapy significantly prolongs the overall survival in high risk of recurrence for MIBC patients after radical cystectomy. For patients intolerant to platinum-based chemotherapy or refusing platinum-based adjuvant chemotherapy, immunotherapy with checkpoint inhibitors combined with albumin-bound paclitaxel can be considered as an effective and well-tolerated adjuvant treatment after radical cystectomy.

Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on MASLD. Methods: Drug target chips and bioinformatics analysis were combined in this study to explore the potential therapeutic effects of ursolic acid on MASLD. Molecular docking simulations, surface plasmon resonance analyses, pull-down experiments, and co-immunoprecipitation assays were used to verify the direct interactions. Gene knockdown mice were generated, and high-fat diets were used to validate drug efficacy. Furthermore, initial CD4+ T cells were isolated and stimulated to demonstrate our findings. Results: In this study, the multifunctional extracellular matrix phosphorylated glycoprotein secreted phosphoprotein 1 (SPP1) was investigated, highlighting its capability to induce Th17 cell differentiation, amplifying inflammatory cascades, and subsequently promoting the evolution of MASLD. In addition, this study revealed that in addition to the canonical TGF-β/IL-6 cytokine pathway, SPP1 can directly interact with ITGB1 and CD44, orchestrating Th17 cell differentiation via their joint downstream ERK signaling pathway. Remarkably, ursolic acid intervention notably suppressed the protein activity of SPP1, suggesting a promising avenue for ameliorating the immunoinflammatory trajectory in MASLD progression. Conclusions Ursolic acid could improve immune inflammation in MASLD by modulating SPP1-mediated Th17 cell differentiation via the ERK signaling pathway, which is orchestrated jointly by ITGB1 and CD44, emerging as a linchpin in this molecular cascade.