To investigate the effect of mesenchymal stromal cells (MSCs) on the fibrosis progression and endometrial regeneration in mouse models of endometrial injury, a mouse endometrial injury model was established by physical scraping combined with lipopolysaccharide (LPS) chemical induction, and the endometrium morphology and collagen deposition were evaluated by HE and Masson staining after unilateral administration of MSCs. RT-qPCR and immunofluorescence were used to detect the expression of epithelial markers Epcam and collagen I (Col1). Primary endometrial epithelial cells were isolated to assess p21 expression. Fibrosis-related genes and signaling pathways were validated using transcriptome sequencing and RT-qPCR. The experimental results showed that MSCs increased endometrial thickness and number of glands (P<0.05), up-regulated the expression of Epcam (P<0.01), while significantly reducing uterine collagen fiber deposition (P<0.05) and the expression of p21 in primary epithelial cells (P<0.0001). Transcriptomic analysis revealed that MSCs attenuated collagen deposition by modulating genes involved in the TGF-β signaling pathway. This study elucidates that MSCs facilitate uterine repair by reversing endometrial fibrosis and promoting epithelial regeneration, and their role is related to the regulation of the TGF-β/SMAD pathway and suppression of aberrant collagen accumulation.

Foot-and-mouth disease (FMD) is one of the major animal infectious diseases in the world. All cloven-hoofed animals are susceptible to FMD. Vaccination is still the first choice for the prevention and control of FMD. mRNA vaccines can be rapidly designed, synthesized, and produced on a large scale in vitro, and they can induce effective protective immune responses, demonstrating the advantages of rapid development, easy preparation, and low biosafety risks. The design of untranslated regions is a key to enhancing the expression and efficacy of mRNA vaccines. In order to generate an efficient FMD mRNA vaccine, we designed three FMD P12A3C expression vectors with different untranslated regions and synthesized corresponding mRNAs. By comparing expression efficiency of these vectors and their mRNAs at different time points and in different cell lines, we found that the mRNA P12A3C-UTR3 had the best expression and universality. This study laid a foundation for the development of mRNA vaccines against FMD and provided a theoretical basis for the optimal sequence design of efficient mRNA.
Foot-and-Mouth Disease Virus/genetics* ; Animals ; RNA, Messenger/biosynthesis* ; Foot-and-Mouth Disease/immunology* ; Antigens, Viral/biosynthesis* ; Viral Vaccines/biosynthesis* ; Genetic Vectors/genetics* ; Cell Line ; Vaccines, DNA/immunology*

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

Vaccination is a crucial strategy for the prevention and control of infectious diseases. Virus-like particles (VLPs), composed of structural proteins, have garnered significant attention as a novel type of vaccine due to their excellent safety and immunogenicity. However, similar to most vaccine antigens, VLPs exhibit insufficient thermal stability, which not only restricts the widespread application of vaccines but also increases the risk of vaccine inactivation. This study aims to enhance the stability and shelf life of VLPs derived from type A foot-and-mouth disease virus (FMDV) by employing vacuum freeze-drying technology. The optimal lyoprotectant formulation was determined through single-factor and combinatorial screening. Subsequently, the correlation between the immunogenicity of the freeze-dried vaccine and the content of FMDV VLPs was evaluated via a mouse model. The stability of FMDV VLPs before and after freeze-drying was further assessed by storing them at 4, 25, and 37 ℃ for varying time periods. Results indicated that the lyoprotectant formulation No.1, composed of 7.5% trehalose, 0.1% Tween 80, 50 mmol/L glycine, 1% sodium glutamate, and 3% polyvinylpyrrolidone (PVP), effectively preserved the content of FMDV VLPs during the vacuum freeze-drying process. The immunization trial in mice revealed that the levels of specific antibodies, immunoglobulin G1 (IgG1), interleukin-4 (IL-4), and neutralizing antibodies induced by freeze-dried FMDV VLPs were comparable to those induced by non-freeze-dried FMDV VLPs. The heat treatment results showed that the storage periods of freeze-dried FMDV VLPs at 4, 25, and 37 ℃ were significantly longer than those of non-freeze-dried FMDV VLPs. In conclusion, the selected lyoprotectant formulation effectively improved the stability of FMDV VLPs vaccines. This study provides valuable insights for enhancing the stability of novel subunit vaccines.
Freeze Drying/methods* ; Animals ; Foot-and-Mouth Disease Virus/immunology* ; Mice ; Vaccines, Virus-Like Particle/chemistry* ; Foot-and-Mouth Disease/immunology* ; Vacuum ; Drug Stability ; Mice, Inbred BALB C ; Viral Vaccines/immunology*

Objective:To explore the effectiveness of family-based interventions for adolescent suicide pre-vention using meta-analytic methods.Methods:A meta-analysis was conducted by searching CNKI,VIP,Wanfang,Web of Science,PubMed,APA PsycInfo and The Cochrane Library for randomized controlled trials of family-based interventions for adolescent suicide prevention.Results:A total of 15 RCTs involving 2541 cases were conclu-ded.The results of meta-analysis showed that family-based therapy was effective in preventing adolescent suicide(95％CI:-0.76--0.09,P＜0.05),with a medium effect size for the intervention(g=-0.42),in which there was a significant effect on reducing suicidal ideation(SMD=-0.77,95％CI:-1.31--0.23,P＜0.05),and the effect on reducing suicide attempts was not significant(OR=0.87,95％CI:0.68-1.11,P＞0.05).Family-based therapies were most effective in adolescent suicide prevention when the duration of the intervention was 12 weeks or more,when they were based on attachment-based family therapy(ABFT)or resource support and safety plans,and when they had a reasonably high dropout rate(Ps＜0.05).Conclusion:Family-based therapy has significant inter-vention effects on adolescent suicide prevention,and intervention effects on suicidal ideation are superior to those on suicide attempts.

Oral diseases have become a major global public health issue. The "Global strategy and action plan on oral health (2023-2030)" issued by the World Health Organization in 2023 marks a milestone in advancing global oral health and serves as a pivotal initiative for implementing global oral health resolutions and strategies. Centered on universal health coverage, the action plan outlines multiple strategies and concrete actions, including strengthening prevention, early intervention, and integrated management, for improving the oral health worldwide. This paper provides a comprehensive review of the strategies and measures outlined in the action plan, aiming to offer valuable insights for developing an oral health pathway in China that aligns with national circumstances and the broader trajectory of human societal development.

Triggering receptor expressed on myeloid cells 2 (TREM2)-mediated microglial phagocytosis is an energy-intensive process that plays a crucial role in amyloid beta (Aβ) clearance in Alzheimer's disease (AD). Energy metabolic reprogramming (EMR) in microglia induced by TREM2 presents therapeutic targets for cognitive impairment in AD. Jiawei Xionggui Decoction (JWXG) has demonstrated effectiveness in enhancing energy supply, protecting microglia, and mitigating cognitive impairment in APP/PS1 mice. However, the mechanism by which JWXG enhances Aβ phagocytosis through TREM2-mediated EMR in microglia remains unclear. This study investigates how JWXG facilitates microglial phagocytosis and alleviates cognitive deficits in AD through TREM2-mediated EMR. Microglial phagocytosis was evaluated through immunofluorescence staining in vitro and in vivo. The EMR level of microglia was assessed using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) kits. The TREM2/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway was analyzed using Western blotting in BV₂ cells. TREM2^-/- BV₂ cells were utilized for reverse validation experiments. The Aβ burden, neuropathological features, and cognitive ability in APP/PS1 mice were evaluated using ELISA kits, immunohistochemistry (IHC), and the Morris water maze (MWM) test. JWXG enhanced both the phagocytosis of EMR disorder-BV₂ cells (EMRD-BV₂) and increased EMR levels. Notably, these effects were significantly reversed in TREM2^-/- BV₂ cells. JWXG elevated TREM2 expression, adenosine triphosphate (ATP) levels, and microglial phagocytosis in APP/PS1 mice. Additionally, JWXG reduced Aβ-burden, neuropathological lesions, and cognitive deficits in APP/PS1 mice. In conclusion, JWXG promoted TREM2-induced EMR and enhanced microglial phagocytosis, thereby reducing Aβ deposition, improving neuropathological lesions, and alleviating cognitive deficits.
Drugs, Chinese Herbal/pharmacology* ; Microglia/drug effects* ; Phagocytosis ; Cognitive Dysfunction/drug therapy* ; Metabolic Reprogramming ; Animals ; Mice ; Cell Line ; Receptors, Immunologic/metabolism* ; Membrane Glycoproteins/metabolism* ; Signal Transduction ; Amyloid beta-Peptides/metabolism* ; Energy Metabolism

Robotic surgery, as an increasingly widespread application in the treatment of gastric and colorectal cancer, still faces obvious discrepancies in recommendations, indications, and evidence strength across existing guidelines. This study systematically analyzed 31 relevant guidelines and consensus statements (retrieved from Chinese and English databases from January 2010 to May 2025) from two dimensions: feasibility (effectiveness, safety, etc.) and training quality control.The results showed that colorectal cancer guidelines had a higher proportion (4 guidelines) of "clear recommendations" for robotic surgery, while gastric cancer guidelines predominantly presented "conditional recommendations" or no recommendations. In the training and quality control dimension, although structured suggestions received positive recommendations, more than half were based on low or very low-quality evidence. Evidence mapping indicated insufficient matching between "case-specific recommendations" and evidence grades in the feasibility dimension, while training processes emphasized the importance of standardized systems and team collaboration.The study highlights the existing heterogeneity in evidence-based guidelines for robotic gastrointestinal surgery, with colorectal cancer demonstrating a more mature evidence base and gastric cancer showing notable evidence gaps. It is recommended that future guideline development should strengthen the consistency between recommendation grades and evidence levels, promote high-quality research in upper gastrointestinal surgery, and improve surgeon training and certification systems to facilitate standardized clinical translation of robotic gastrointestinal surgery.

Objective: To analyze the factors associated with high level fear of negative evaluation (FNE) among junior high school students and to construct a nomogram risk prediction model, so as to provide scientific tools for psychological health intervention for junior high school students. Methods: A convenience sampling combined with cluster random sampling method was used to select 5 485 junior high school students from 4 cities (Wuhan, Huanggang, Xianning and Xiaogan) for an online questionnaire survey in March 2025. The total sample was randomly split into a training set ( n =3 839) and a validation set ( n =1 646). Univariate analysis was performed in the training set using Chi-square test and t-test. Variables with statistical significance were subsequently included in multivariate Logistic regression to identify independent predictors and to construct a nomogram based risk prediction model. The discriminative ability and clinical utility of the model were evaluated in the validation set using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Results: There were 1 649 junior high school students with low level FNE and 2 190 with high level FNE in the training set. The self control ability of junior high school students with lowlevel and high level FNE showed a statistically significant difference (23.96±3.96, 21.48±3.37, t=25.15, P < 0.01 ). Statistically significant differences in the detection rate of high level FNE were observed among junior high school students with different genders, family types, parenting styles, academic rankings, psychological flexibility, mobile phone addiction tendencies, emotional management training, exercise frequency, left behind experiences, and places of origin ( χ 2=82.01- 1 126.68 , all P <0.01). The results of Logistic regression analysis revealed that, the following factors were identified as significant factors influencing high level FNE among junior high school students:exercise frequency ( OR=0.21, 95%CI =0.17-0.26); parenting style ( OR=0.48, 95%CI =0.40-0.58); left behind experience ( OR=3.88, 95%CI =3.27-4.61); smartphone addiction proneness ( OR=2.19, 95%CI =0.89-0.93); self-control ability ( OR=0.91, 95%CI =0.89-0.93); and psychological flexibility ( OR=0.16, 95%CI =0.10-0.28) (all P <0.05). The AUC for the training and validation set were 0.88 (95% CI =0.87-0.89) and 0.87 (95% CI =0.85-0.89), respectively. The Hosmer-Lemeshow goodness of fit test yielded χ 2=8.57, 15.20 (both P >0.05). Conclusion The risk prediction model with high level FNE demonstrates good accuracy and can assist educators and parents in timely screening of junior high school students with high level FNE, thereby providing a basis for implementing targeted interventions.

Objective The study aims to investigate the immunological functions of the nucleocapsid (N) protein of the novel coronavirus Omicron (BA.1, BA.2) and evaluate the differences among different N proteins of mutant strains in immunogenicity. Methods By aligning sequences, the mutation sites of the Omicron (BA.1, BA.2) N protein relative to prototype strain of the novel coronavirus (Wuhan-Hu-1) were determined. The pET-28a-N-Wuhan-Hu-1 plasmid was used as template to construct pET-28a-BA.1/BA.2-N through single point mutation or homologous recombination. The three kinds of N protein were expressed in prokaryotic system, purified through Ni-NTA affinity chromatography, and then immunized into mice. The titer and reactivity of the polyclonal antibody, as well as the expression level of IL-1β and IFN-γ in mouse spleen cells, were detected using indirect ELISA and Western blot assay. Results The constructed prokaryotic expression plasmids were successfully used to express the Wuhan-Hu-1 N, BA.1 N, and BA.2 N proteins in E.coli BL21(DE3) at 37 DegreesCelsius for 4 hours. The indirect ELISA test showed that the titers of polyclonal antibody prepared by three N proteins were all 1:51 200. All three N proteins can increase the expression of IFN-γ and IL-1β cytokines, but the effect of Omicron N protein in activing two cytokines was more obvious than that of Wuhan-Hu-1 N protein. Conclusion The study obtained three new coronavirus N proteins and polyclonal antibodies, and confirmed that mutations in the amino acid sites of the N protein can affect its immunogenicity. This provides a basis for developing rapid diagnostic methods targeting N protein of different novel coronavirus variants.
Animals ; Mice ; SARS-CoV-2/genetics* ; Coronavirus Nucleocapsid Proteins/immunology* ; Nucleocapsid Proteins/isolation & purification* ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Mice, Inbred BALB C ; Interferon-gamma/metabolism* ; Interleukin-1beta/metabolism* ; Female ; Escherichia coli/metabolism* ; Mutation ; Humans