Breast cancer is a kind of malignant tumor with a complex mechanism， and its morbidity and mortality are increasing year by year， which seriously threatens women's health. At present， the main clinical treatments are surgical resection， radiotherapy， chemotherapy， and drug therapy， but they are often accompanied by side effects and adverse reactions， which affect the therapeutic effect. Traditional Chinese medicine （TCM） has the advantages of multi-component and multi-target treatment in the fight against breast cancer. The wnt/β-catenin signaling pathway is one of the classic pathways in cancer research. Abnormally activated Wnt/β-catenin signaling pathway inhibits β-catenin degradation by blocking the formation of Axin/glycogen synthase kinase 3β/adenomatous polyposis coli complex， thus promoting β-catenin nuclear metastasis， and it binds to T cell transcription factor/lymphoenhancer factor-1 to initiate downstream target genes and further interfere with the proliferation， migration， and invasion of tumor cells to affect the tumor process. Previous studies have shown that TCM monomers and compounds can mediate the Wnt/β-catenin signaling pathway to inhibit the malignant phenotype of breast cancer cells， thus playing an anti-breast cancer role， and the biochemical process involved in the regulation of therapeutic drugs has not been systematically combed. By analyzing and collating Chinese and foreign literature at the present stage， this paper discussed the association mechanism between Wnt/β-catenin signaling pathway and breast cancer and analyzed the internal mechanism of TCM monomers and compounds in mediating Wnt/β-catenin signaling pathway to exert anti-breast cancer effect. The statistical results showed that the flavonoids， alkaloids， and terpenoids in TCM monomers could target the Wnt/β-catenin signaling pathway and block the further development of malignant phenotype of breast cancer cells. TCM compounds with functions of clearing heat and detoxifying， promoting blood circulation and removing blood stasis， and tonifying kidney and liver were commonly used to intervene in the Wnt/β-catenin signaling pathway to prevent breast cancer. Compared with the current inhibitors of Wnt/β-catenin signaling pathway， the application of TCM monomers and compounds is expected to bring low-toxicity and high-efficiency breast cancer treatment drugs to the clinical practice， and the existing results provide a reference for the subsequent screening， research， and development of TCM small-molecule compounds and TCM compounds against breast cancer.

Objective: To analyze the characteristics of road traffic injuries (RTI) among urban and rural residents in Zhejiang Province, so as to provide a basis for developing targeted RTI prevention and control strategies. Methods: In April 2023, permanent residents from 13 counties (cities, districts) in Zhejiang Province were selected using a multistage stratified random sampling method. Basic information and RTI occurrences within the past 12 months were collected through questionnaire surveys. RTI incidence and characteristics of RTI among urban and rural residents were analyzed. Results: A total of 36 980 individuals were surveyed, including 18 327 males (49.56%) and 18 653 females (50.44%). The median age was 56.00 (interquartile range, 28.00) years. There were 442 person-times of RTI, with an incidence of 1.20%. The rural incidence was significantly higher than the urban (1.33% vs. 1.05%, P<0.05). The incidence of RTI increased with age and decreased with higher educational attainment (both P<0.05). The majority of RTI occurred on streets/urban areas, accounting for 59.28%. In urban, streets/urban areas were the primary locations, accounting for 76.84%. In rural, streets/urban areas and intercity highways were the main sites, accounting for 46.03% and 40.48%, respectively. There was a statistically significant difference in the composition of RTI locations between urban and rural (P<0.05). The primary treatment approach of RTI was outpatient/emergency care, accounting for 61.99%. There was a statistically significant difference in the proportion of treatment approaches of RTI between urban and rural (P<0.05). Electric bicycles were involved in 67.87% of RTI, and 54.29% of motor vehicle occupants used seat belts. No statistically significant differences were observed in the composition of transportation modes or seat belt usage rates between urban and rural (both P>0.05). The lower limb was the most commonly injured sites, accounting for 42.31%. Mild injury was predominant, accounting for 50.90%, and complete recovery was predominant outcome, accounting fo 69.68%. The median rest period was 13.50 (interquartile range, 27.25) days. The median medical expenses was 1 200.00 (interquartile range, 5 700.00) yuan. No statistically significant differences were observed between urban and rural in terms of injury sites, injury severity, outcome, rest period, or medical expenses (all P>0.05). Conclusions RTI incidence is higher among rural residents, the elderly, and lower education levels residents in Zhejiang Province. It is recommend optimizing road safety infrastructure on streets/urban areas and intercity highways, prioritizing prevention of electric bicycles RTI, strengthening safety education for high-risk population, and increasing the usage rate of safety devices.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective To generate and characterize natural killer cell (NK cell)-conditional Cd226 gene knockout mice using Cre-loxP technology, and to explore the role of CD226 on NK cells in alleviating intestinal inflammation in a murine model of ulcerative colitis (UC). Methods NK cell-conditional Cd226 gene knockout mice were generated by crossing loxP-flanked Cd226 mice with Ncr1-Cre mice via the Cre-loxP system. Polymerase chain reaction (PCR) and agarose gel electrophoresis were used for genotyping. A UC model was established by dextran sulfate sodium (DSS) induction. Flow cytometry was performed to analyze CD226 expression levels on NK cells and the infiltration of related immune cells in colon tissues. Hematoxylin-eosin (HE) staining was performed to assess the degree of colonic inflammation. Results DNA gel electrophoresis and flow cytometry confirmed the successful generation of NK cell-specific Cd226 knockout mice. After conditional knockout of Cd226 in NK cells, inflammation in the UC mouse model was alleviated. Flow cytometry results showed a reduced proportion of NK cells in peripheral blood and the colon lamina propria, while HE staining demonstrated attenuated inflammatory responses. Conclusion Specific knockout of Cd226 in NK cells mitigates intestinal inflammation in UC mice by reducing NK cell numbers and inhibiting their pro-inflammatory functions.
Animals ; Colitis, Ulcerative/pathology* ; Killer Cells, Natural/metabolism* ; Mice, Knockout ; T Lineage-Specific Activation Antigen 1 ; Antigens, Differentiation, T-Lymphocyte/genetics* ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Male

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Bio-mineralization has emerged as a promising strategy to enhance vaccine immunogenicity. This study optimized the calcium phosphate (CaP) mineralization process of foot-and-mouth disease virus-like particles (FMD VLPs) to achieve high mineralization efficiency and scalability. Key parameters, including concentrations of Ca²⁺, HPO₄^2-, NaCl, and VLPs, as well as stirring speed, were systematically optimized. Stability of the scaled-up reaction system and immunogenicity of the mineralized vaccine were evaluated. Optimal conditions [25.50 mmol/L Ca(NO₃)₂, 15 mmol/L Na₂HPO₄, 300 mmol/L NaCl, 0.75 mg/mL VLPs, and 1 500 r/min] yielded CaP-mineralized VLPs (VLPs-CaP) with high mineralization efficiency, uniform morphology, and a favorable particle size. Scaling up the reaction by 25 folds maintained consistent mineralization efficiency and particle characteristics. Immunization in mice demonstrated that VLPs-CaP induced higher titers of specific antibodies and neutralizing antibodies than unmineralized VLPs (P < 0.05). Higher IgG2a/IgG1 ratio and enhanced IFN-γ secretion (P < 0.05) further indicated robust cellular immune responses. We establish a stable and scalable protocol for VLPs-CaP, providing a theoretical and technical foundation for developing high-efficacy VLPs-CaP vaccines.
Vaccines, Virus-Like Particle/immunology* ; Immunogenicity, Vaccine ; Calcium Phosphates/chemistry* ; Foot-and-Mouth Disease Virus ; Biomineralization ; Particle Size ; Animals ; Mice ; Antibodies, Neutralizing/blood* ; Antibodies, Viral/blood* ; Immunity, Cellular

Objective To compare the efficacy and adherence of rivaroxaban versus low-molecular-weight heparin for prophylactic anticoagulation in cancer patients with venous thromboembolism(VTE).Methods A total of 120 intermediate-to-high VTE risk patients with malignant tumors admitted to Depart-ment of Hematology and Oncology,West China Longquan Hospital of Sichuan University between September 2021 and December 2022,were randomly assigned to the rivaroxaban group(n=60)and the low-molecular-weight heparin group(n=60)using the random number table.The rivaroxaban group received oral Rivaroxa-ban,while the low-molecular-weight heparin group received subcutaneous injections of low-molecular-weight heparin sodium for prophylactic anticoagulation.All patients were followed up for 180 days.The primary end-point was medication adherence.The secondary endpoints included the incidence of VTE,bleeding events,and changes in coagulation parameters.Results The rate of good medication adherence was significantly higher in the rivaroxaban group than in the low-molecular-weight heparin group(95.00％vs.88.33％,P＜0.05).However,there were no statistically significant differences in the incidence of VTE or overall bleeding events between the two groups(P＜0.05).Following treatment,parameters including fibrinogen,prothrombin time(PT),and D-dimer levels showed significant improvement from baseline in both groups.Compared to the low-molecular-weight heparin group,the Rivaroxaban group demonstrated significantly higher fibrinogen levels,shorter PT,and lower D-dimer levels(P＜0.05).Stepwise logistic regression analysis identified the post-treatment platelet(PLT)count as a significant factor influencing bleeding events during prophylactic antico-agulation(P＜0.05).Khorana score≥3(high risk)was identified as a risk factor for bleeding events(P＜0.05).The incidence of clinically relevant non-major bleeding(CRNMB)was higher in the rivaroxaban group[11.67％(7/60)]compared to the low-molecular-weight heparin group[8.33％(5/60)],although the differ-ence was not statistically significant(P＜0.05).Kaplan-Meier curve analysis revealed no significant difference in the cumulative incidence of bleeding-free events between the two groups(P＜0.05).Conclusion Oral ri-varoxaban and subcutaneous low-molecular-weight heparin demonstrate comparable efficacy and safety for VTE prevention in cancer patients,but rivaroxaban significantly improves patient's adherence.

Objective To investigate the correlation between peripheral blood syndecan-1(SDC-1)and ma-londialdehyde-modified low-density lipoprotein(MDA-LDL)with arteriosclerosis(AS)in hemodialysis pa-tients and their clinical predictive value.Methods A total of 125 hemodialysis patients admitted to the hospi-tal from January 2022 to June 2024 as the hemodialysis group,and 65 healthy individuals who underwent physical examination during the same period as the control group.According to whether AS occurred,hemodi-alysis patients were divided into AS group(65 cases)and non-AS group(60 cases).The levels of SDC-1 and MDA-LDL in peripheral blood were detected by enzyme-linked immunosorbent assay.The correlation between the levels of SDC-1 and MDA-LDL in peripheral blood of hemodialysis patients and brachial-ankle pulse wave velocity(baPWV)was analyzed by Spearman correlation analysis.Multivariate unconditional Logistic regres-sion was used to determine the relationship between the levels of SDC-1 and MDA-LDL in peripheral blood and AS in hemodialysis patients.The receiver operating characteristic(ROC)curve was used to analyze the pre-dictive efficacy of peripheral blood SDC-1 and MDA-LDL levels for AS in hemodialysis patients.Results Compared with the control group,the levels of SDC-1 and MDA-LDL in the peripheral blood of the hemodialysis group increased(P＜0.05).The levels of SDC-1 and MDA-LDL in the peripheral blood of hemodialysis patients were positively correlated with left baPWV and right baPWV(P＜0.05).High SDC-1 and high MDA-LDL were both independent risk factors for AS in hemodialysis patients(P＜0.05).The area under the curve for the combined prediction of AS in hemodialysis patients by peripheral blood SDC-1 and MDA-LDL levels was 0.858,which was greater than 0.785 and 0.778 predicted separately by peripheral blood SDC-1 and MDA-LDL levels(P＜0.05).Conclusion The increase of SDC-1 and MDA-LDL levels in peripheral blood of hemodialy-sis patients is closely related to AS,and the combination of SDC-1 and MDA-LDL levels in peripheral blood has a higher energy efficiency in predicting AS.

Objective:To explore the effectiveness of patient participation and Internet plus in fall prevention management strategies of elderly inpatients and analyze the causes of falls, so as to provide a basis for continuous improvement in fall prevention to investigate their continuous improvement.Methods:A pre- and post-control study was conducted. Totally 8 480 elderly inpatients hospitalized in the Department of Internal Medicine from 1 June 2020 to 31 May 2021 in Chenzhou NO. 1 People′s Hospital were selected by convenient sampling as the control group, and 8 662 elderly inpatients hospitalized in the Department of Internal Medicine from 1 June 2021 to 31 May 2022 were in the experimental group. The routine fall prevention measures were used in the control group, and on this basis, the experimental group formulated and implemented fall prevention management strategies involving patients based on the patient participation framework "informing, participating, empowering, cooperating, and electronic information support" and introduced Internet plus. Then the differences between the two groups in terms of the incidence of falls and the satisfaction rate of nursing care were compared.Results:The experimental group included 8 662 cases (5 110 males and 3 552 females) with (73.96 ± 8.78) years old, while the control group included 8 480 cases (4 918 males and 3 562 females) with (74.11 ± 8.59) years old. The incidence of falls in experimental group (0.092%, 8/8 662) was lower than that in control group (0.224%, 19/8 480), and the difference was statistically significant ( χ 2=4.71, P<0.05); the nursing care satisfaction rate of experimental group (98.880%, 8 565/8 662) was higher than that of control group (96.450%, 8 179/8 480), and the difference also was statistically significant ( χ 2=106.50, P<0.01); the analysis of the fall causes of the patients revealed that the toilet squatting commode was an important hidden risk of falls in elderly patients. Conclusions:Fall prevention management strategies based on patient participation can reduce the incidence of falls in elderly patients and improve the satisfaction rate of nursing care. Patient participation introduced "Internet plus" can prevent patient falls. The root causes of patient falls will continue to change, and care managers should continually track real-time changes in the root causes of falls to identify problems, develop and adjust prevention strategies accordingly, and pay attention to the importance of infrastructure in the safety of older patients.