Objective: To understand the allocation and use of safety seats for preschool children and explore its related factors, so as to provide a scientific reference for promoting the usage of safety seats. Methods: A stratified random cluster sampling method was used to select 3 143 parents of preschool children aged 3 to 6 from six kindergartens in Shunyi District, Beijing from January 3 to 10, 2022. An online questionnaire survey was conducted to collect and evaluate the equipment and use of child safety seats in different characteristics of preschool children, as well as their scores of health beliefs. Multiple factor Logistic regression analysis was used to investigated the related factors of safety seat configuration and use. Results: The equipping rate and usage rate of safety seats for preschool children were 66.56% and 58.45%, respectively. The proportion of equipped and used safety seats for preschool children in core families (69.52%, 62.23%) were higher than that in large families (64.35%, 55.62%), only child families ( 72.39 %, 64.87%) were higher than non only child families (61.49%, 52.86%), and urban families (71.63%, 63.04%) were higher than rural families (52.31%, 45.51%) ( χ 2=9.23, 13.86; 41.72, 46.44; 101.96 ,76.97,all P <0.05) . As the educational level of parents ( χ 2 trend =154.23,98.76) and annual income of the family ( χ 2 trend =155.78,127.69) rised, the reporting rates of the equipped and used child safety seats in the family also increased(all P <0.05 ). There were statistically significant differences in the scores of different dimensions of health beliefs for the provision ( t =-20.22-18.16) and use ( t =24.32-24.17) of safety seats for preschool children(all P <0.05). After adjusting for child sex, child age, family annual income, parental education level, family type, whether the child was an only child, and place of residence，multivariate Logistic regression analysis showed that preschool children with higher perceived susceptibility score( OR =1.11, 1.08), higher self efficacy score( OR =1.23, 1.33), and higher suggestive factors score( OR =1.08, 1.12) were more likely to have and use safety seats in their families, while preschool children with higher perceived impairments score( OR =0.82, 0.80) were less likely to have and use safety seats in their families (all P <0.05). Conclusions The installation rate of child safety seats needs to be improved, and there is also a certain gap in their use after installation. Parents of preschool children should improve susceptibility and self efficacy to safety seat equipment and use, and perceptual barriers should be reduced.

Objective: To investigate the effect of targeted silencing of DNA methyltransferase 3A(DNMT3A) on collagen deposition, proliferation and migration activity of mouse lung fibroblasts(PFs). Methods: In order to ensure the proliferation and migration activity of primary fibroblasts, the lung tissues of neonatal C57 suckling mice were taken, PFs were extracted after being sheared, and the morphology was observed and identified under the microscope. PFs cells were activated by 5 ng/ml TGF-β1for 24 h after cell attachment, and DNMT3A silencing model was constructed by small interfering RNA; The experiment was divided into control group, TGF-β1group, TGF-β1+ siRNA-NC group and TGF-β1+ siRNA-DNMT3A group. The protein expressions of DNMT3A, α-smooth muscle actin(α-SMA) and Collagen Ⅰ were detected by Western blot; Real time quantitative reverse transcription polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression changes ofDNMT3A,α-SMAandCollagenⅠ. The proliferation ability of PFs was detected by CCK-8 and EdU staining; the migration ability of PFs was detected by scratch test and Transwell migration test. Results: Compared with the control group, TGF-β1induced the increase of DNMT3A in the activated PFs cell group(P<0.01), the protein and mRNA levels of fibrosis and proliferation related indicators α-SMA and Collagen Ⅰ also increased(allP<0.05), and the proliferation and migration ability of PFs increased(allP<0.000 1). Compared with the siRNA-NC group, the protein expression levels of DNMT3A(P<0.000 1) and related indicators α-SMA(P<0.01) and Collagen Ⅰ(P<0.01) significantly decreased in the DNMT3A silencing group by Western blot, and the mRNA levels ofDNMT3A,α-SMAandCollagenⅠby RT-qPCR also decreased(allP<0.001), and the proliferation(P<0.01) and migration ability(P<0.05) of PFs cells decreased compared with the control group. Conclusion Silencing DNMT3A can inhibit the deposition of collagen and the proliferation of PFs. DNMT3A can promote the proliferation and migration of PFs, and then promote the activation of PFs and the development of pulmonary fibrosis. This process may be regulated by DNA methylation modification.

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

Thalidomide (THA) is renowned for its potent anti-inflammatory properties. This study aimed to elucidate its underlying mechanisms in the context of Crohn's disease (CD) development. Mouse colitis models were established by dextran sulfate sodium (DSS) treatment. Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry, respectively. Antibiotic-treated mice served as models for microbiota depletion and transplantation. The expression of forkhead box P3⁺ (FOXP3⁺) regulatory T cells (Tregs) was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort. THA inhibited colitis in DSS-treated mice by altering the gut microbiota profile, with an increased abundance of probiotics Bacteroides fragilis, while pathogenic bacteria were depleted. In addition, THA increased beneficial metabolites bile acids and significantly restored gut barrier function. Transcriptomic profiling revealed that THA inhibited interleukin-17 (IL-17), IL-1β and cell cycle signaling. Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA. Specifically, increased level of gut commensal B. fragilis was observed, correlated with elevated levels of the microbial metabolite 3alpha-hydroxy-7-oxo-5beta-cholanic acid (7-ketolithocholic acid, 7-KA) following THA treatment. This microbial metabolite may stable FOXP3 expression by targeting the receptor FMR1 autosomal homolog 1 (FXR1) to inhibit autophagy. An interaction between FOXP3 and FXR1 was identified, with binding regions localized to the FOXP3 domain (aa238-335) and the FXR1 domain (aa82-222), respectively. Conclusively, THA modulates the gut microbiota and metabolite profiles towards a more beneficial composition, enhances gut barrier function, promotes the differentiation of FOXP3⁺ Tregs and curbs pro-inflammatory pathways.

Objective : To clarify the intrinsic link between a high-fat diet(HFD) and the pathological progression and prognosis of spinal cord injury(SCI) while preliminarily exploring the potential underlying mechanisms. Methods: SCI models were established in mice that were fed either a regular diet(RD) or HFD, with injury inflicted specifically on the T9-T12segments. Hematoxylin-Eosin(HE) staining, Masson staining, and Nissl staining were used to observe the local histological changes in SCI tissues. The basso, beattie, and bresnahan(BBB) score and footprint analysis were used to evaluate and compare hindlimb functional recovery after SCI in both RD and HFD mice.In vitroexperiments were conducted to identify key fatty acids in the HFD that exacerbate neuronal damage, whilein vivoexperiments assessed the effects of 2-bromopalmitate(2-BP), a palmitic acid inhibitor, on HFD-fed mice with SCI. Results : Compared to RD-fed mice, HFD-fed mice exhibited significantly larger lesion areas, more severe neuronal damage, and poorer hindlimb functional recovery after SCI. Palmitic acid was identified as the key fatty acid aggravating neuronal damage. Further more, inhibition of palmitoylation, mediated by palmitic acid, enhanced neuronal survival, promoted tissue repair, and improved hindlimb functional recovery in HFD-fed mice post-SCI. Conclusion HFD exacerbates pathological damage following SCI in mice through palmitic acid, impairing recovery. Palmitic acid-mediated palmitoylation is likely the main mechanism underlying this effect.

The SNP loci of ACOX1 gene in 83 China Holstein cows were detected by PCR amplifica-tion and direct sequencing,and the association between the genetic polymorphism loci of ACOX 1 gene and milk quality traits of China Holstein cows was analyzed by SPSS 25.0 software.The re-sults showed that a SNP locus I3-2 267 G→C was found in the third intron of ACOX1 gene,it was moderately polymorphic and in Hardy Weinberg equilibrium in the population.By correlation anal-ysis,it was found that the SNP locus was significantly related to the somatic cell content and cor-rected milk quantity of dairy cows.The I3-2 267 G→C locus of ACOX1 gene can be used as a mo-lecular marker of quality traits of Holstein cows in China,and provide reference for the study of quality traits of Holstein cows in China.

Objective:To analyze the effect of recombinant human thrombopoietin(rhTPO)on platelet(PLT)reconstitution after autologous peripheral blood stem cell transplantation(APBSCT)in patients with multiple myeloma(MM).Methods:The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed.According to whether rhTPO was used during APBSCT,the patients were divided into rhTPO group(80 cases)and control group(67 cases).The time of PLT engraftment,blood product infusion requirements,the proportion of patients with PLT recovery to ≥ 50 × 109/L and ≥ 100 × 109/L at+14 days and+100 days after transplantation,and adverse reactions including the incidence of bleeding were compared between the two groups.Results:There were no significant differences between the two groups in sex,age,M protein type,PLT count at the initial diagnosis,median duration of induction therapy before APBSCT,and number of CD34+cells reinfused(all P＞0.05).The median time of PLT engraftment in the rhTPO group was 10(6-14)days,which was shorter than 11(8-23)days in the control group(P＜0.001).The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U,which was less than 20(0-80)U in the control group(P=0.001).At+14 days after transplantation,the proportions of patients with PLT 2 50 × 109/L in the rhTPO group and the control group were 66.3％and 52.2％,while the proportions of patients with PLT ≥ 100 × 109/L were 23.8％and 11.9％,respectively,with no significant differences(all P＞0.05).At+100 days after transplantation,the proportion of patients with PLT ≥ 50 × 109/L in rhTPO group and control group was 96.3％and 89.6％,respectively(P＞0.05),but the proportion of patients with PLT ≥ 100 × 109/L in rhTPO group was higher than that in control group(75.0％vs 55.2％,P=0.012).There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups.In rhTPO group,the rhTPO administration was well tolerated,and the incidences of abnormal liver and kidney function and infection were similar to those in the control group.Conclusion:When MM patients undergo first-line APBSCT,subcutaneous injection of rhTPO can shorten the time of platelet engraftment,reduce the transfusion volume of blood products,and be well tolerated,moreover,more patients have achieve a high level of PLT recovery after transplantation,which is very important for ensuring the safety of APBSCT and maintenance therapy.

Objective:To summarize and analyze the composition characteristics and problems of basic medical insurance policies for traditional Chinese medicine in various provinces of China,providing reference for optimizing and improving subsequent basic medical insurance policies for traditional Chinese medicine.Methods:Based on the perspective of policy instrument,combined with two dimensions of policy instrument types and policy development process,the content analysis method is used to quantitatively analyze the content of the basic medical insurance policies for traditional Chinese medicine released at the provincial level from 2011 to 2023.Results:The 93 included policy documents were coded and sorted,with a cumulative total of 487 codes.From the perspective of policy instrument dimensions,subcategories of policy instruments involve diverse themes,but there are differences in the level of attention paid to each policy tool.From the perspective of policy development process,each link also presents a discrete trend,indicating a dominant feature of policy planning and implementation.Conclusion:To improve the basic medical insurance policy system of traditional Chinese medicine in China,it is necessary to optimize the combination of policy instrument and construct a coordinated and balanced policy instrument framework;Overall planning of the development process of traditional Chinese medicine medical insurance policies,highlighting the unique advantages of traditional Chinese medicine;Emphasize policy synergy between dimensions and strengthen the implementation of traditional Chinese medicine medical insurance policies.