Objective: To systematically evaluate the association between maternal adverse childhood experiences (ACEs) and offspring social behavior, so as to provide a theoretical basis for further research on intergenerational social behavioral development. Methods: Relevant research literature about maternal ACEs and the development of children s maladaptive social behaviors were collected, from China National Knowledge Infrastructure (CNKI), VIP, Wanfang, SinoMed, PubMed, Web of Science, Cochrane Library, Embase and SpringLink databases, covering the period from the inception of each database to May 2025. The Chinese database matched and searched through three groups of keywords: "Pregnant women" "Mothers" and "Women"; "Bad childhood experience" "Bad early experience" and "Bad adolescent experience"; "Children" "Teenagers" "Children s behavior" "Children s development" "Teenagers behavior" "Internalized behavior" and "Externalized behavior". The English database was searched by three groups of keywords: "Female" "Pregnant women" "Mothers"; "Adverse childhood experiences" "Adverse early childhood experiences" "Adverse experiences of adolescent"; "Child behavior" "Child development" "Adolescent behavior" "Internalized behaviors" "Externalized behaviors". The selected literature was evaluated for quality and data extraction, with OR and 95% CI as effect indicators. Stata 16.0 software was used for heterogeneity testing, subgroup analysis, and publication bias analysis. Results: A total of 14 studies involving 64 302 mother-child pairs were included. The Meta analysis results showed a significant correlation between maternal ACEs and both offspring maladaptive internalized behaviors ( OR=1.75, 95%CI=1.42-2.15, P <0.01) and externalized behaviors ( OR=1.82, 95%CI=1.51-2.20, P <0.01). The results of subgroup analyses showed that in different regions[internalized behaviors:domestic, foreign OR (95% CI )=2.03(1.49-2.76), 1.55(1.19-2.03); externalized behaviors: domestic, foreign OR (95% CI )=2.41(1.52-3.82), 1.65(1.36-2.01)], study type[internalized behaviors: cohort study, cross sectional study OR (95% CI )=1.64(1.34-2.00), 1.85(1.30-2.65); externalized behaviors: cohort study, cross sectional study OR (95% CI )=1.76(1.46-2.12), 2.12(1.40-3.20)], sample size [internalized behaviors: ≥4 000, <4 000 pairs OR (95% CI )=1.69(1.13-2.55), 1.77( 1.41 -2.24); externalized behaviors: ≥3 000, <3 000 pairs OR (95% CI )=1.72(1.37-2.17), 2.13(1.44-3.15)], there were significant and positive association between mothers ACEs and children s internalizing and externalizing behaviors (all P <0.05). Conclusion A substantial positive association exists between maternal ACEs and the development of offspring maladaptive internalized and externalized behaviors, but the result needs to be continued to be validated by more research.

OBJECTIVE: To investigate the impact of different iterative cone beam CT (iCBCT) scanning beam currents from a ring-mounted linac on synthetic CT image quality for lung adaptive radiotherapy under lung scanning protocol. METHODS: The CIRS lung motion phantom was configured to simulate conventional respiratory motion pattern, followed by 4D-CT simulation. After transferring the radiotherapy plan to the ring-mounted Halcyon 3.0 linac, three groups of typical iCBCT scans with different beam currents [ I _low (160 mA), I _middle (282 mA), and I _high (491 mA)] were performed and corresponding image reconstructions were completed. Synthetic CT (sCT) images were subsequently obtained based on the deformable registration algorithm. RESULTS: Compared to the corresponding CBCT images, the sCT images exhibited a significant reduction in artifacts. The fine structure of the planning CT (pCT) image was preserved for sCT images corresponding to different scanning beam currents, with Dice similarity coefficients exceeding 0.90 for all cases. CONCLUSION The image quality of sCT corresponding to different iCBCTs is comparable to that of pCT, and changes in iCBCT beam parameters have a negligible impact on sCT image quality. Taking into account both image quality and imaging dose factors associated with the beam currents, iCBCT with a lower beam current on the ring-mounted Halcyon linac offers greater clinical value in lung adaptive radiotherapy.
Cone-Beam Computed Tomography/methods* ; Phantoms, Imaging ; Humans ; Radiotherapy Planning, Computer-Assisted/methods* ; Lung/diagnostic imaging* ; Lung Neoplasms/diagnostic imaging*

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

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.

Objective: To investigate the effects of β-caryophyllene(BCP) on the browning of white adipose tissue in obese mice and the related mechanisms. Methods: An obese mouse model was establishedviaintraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution [14.4 mg/(kg·d)] in male Kunming mice. Obesity model mice were randomly divided into a model group(Model group) and a BCP administration group(BCP-50 group); normal diet mice were set up as a control group(Control group), with 8 mice in each group. BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group, while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks. The oral glucose tolerance test was performed at the end of 4-week administration, and mice were executed after overnight fasting at the end of the experiment, and blood samples and adipose tissues were rapidly collected for subsequent experimental tests. The kit was used to detect serological-related indexes; hematoxylin-eosin staining was conducted to observe the morphology of adipose tissue; immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1) in adipose tissue; Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α), peroxisome proliferator-activated receptor γ(PPARγ), UCP1 and cannabinoid receptor 2(CNR2) proteins in epididymal white adipose(eWAT). Results: Compared with the model group, the body mass of obese mice in the BCP-50 group was significantly reduced(P<0.05), food intake was decreased(P<0.01), insulin resistance was improved(P<0.000 1), and the serum content of low-density lipoprotein cholesterol(LDL-C) and nonesterified fatty acid(NEFA) in the obese mice was significantly reduced(P<0.000 1 andP<0.01). Total cholesterol(TC), triglyceride(TG), and high-density lipoprotein cholesterol(HDL-C) contents did not change significantly. In addition, the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P<0.05); the adipocytes in eWAT and BAT were reduced; and the expression of the UCP1 protein was significantly elevated(P<0.01 andP<0.05). In addition to UCP1, the expression levels of PGC1α, PPARγ, and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P<0.01,P<0.05, andP<0.001). Conclusion β-caryophyllene promotes white adipose tissue browning through up-regulating PPARγ/PGC-1α/UCP1 pathway expression, thus improving obesity.

Objective: To construct an evaluation index system of oral health literacy for children's parents, so as to provide an index system for the evaluation of oral health literacy for children's parents in China. Methods: The evaluation index system of oral health literacy for children's parents was designed based on literature review and semi-structured interview. Experts from oral prevention and pediatric oral medicine were invited to participate in two-round Delphi consultations. The indicators were scored and screened according to the importance, and the weight determined using analytic hierarchy process. The effectiveness of the consultation was evaluated by positive coefficient, authority coefficient and coordination coefficient. Results: Twenty-four experts participated in the consultation, including 6 males and 18 females. There were 21 experts with a master degree, 3 experts with a doctor degree, and 20 experts with vice senior professional titles and above. The recovery rates of the two rounds of consultations were 96.00% and 100.00%, the authority coefficients were 0.866 and 0.917, the Kendall's coefficient of concordance were 0.120 and 0.156 (both P<0.05), and the coefficient of variation was 0.15-0.38 and 0.03-0.17, respectively. The final evaluation index system included 3 primary indicators, 11 secondary indicators and 40 tertiary indicators. The primary indicators were basic knowledge and concepts related to oral health, promoting lifestyle and behaviors related to oral health, and maintaining basic skills related to oral health. Conclusion The evaluation index system of oral health literacy for children's parents has been established in this study and needs to be further applied and evaluated.

Objective:To discuss the effect of adipose-derived stem cell-derived exosomes(ADSC-Exos)on the migration ability of the macrophages RAW264.7,and to clarify its role in promoting function of the macrophages.Methods:The adipose tissue adjacent to epididymis of the SD rats was isolated to perform primary culture of the adipose-derived stem cells(ADSCs).The adipogenic and osteogenic differentiation induction was conducted,and the multidirectional differentiation potential of the ADSCs was detected by oil Red O and Alizarin red staining.Western blotting and immunofluorescence methods were used to detect the positive expressions of the ADSCs markers CD29 and CD44;the ADSC-Exos were extracted by Exos isolation kit,and the morphology,size,and distribution of particle size of the ADSC-Exos were examined by transmission electron microscope and nanoparticle tracking analyzer;the expression levels of exosome-specific markers CD9 and TSG101 proteins in the ADSC-Exos were detected by Western blotting method;the uptake of ADSC-Exos by the macrophages was observed by tracing method.The macrophages RAW264.7 were divided into control group,10 mg·L-1 ADSC-Exos group,20 mg·L-1 ADSC-Exos group,and 40 mg·L-1 ADSC-Exos group.The activities of the macrophages in various groups were detected by 5-ethynyl-2'-deoxyuridine(EdU)staining;the number of migration macrophages in various groups was detected by Transwell chamber assay;the adhesion of macrophages in various groups was observed by fluorescence microscope.Results:After 24 h of primary culture,the ADSCs adhered to the wall and exhibited scattered,elongated shapes;after 7 d of culture,the adherent cells showed a comb-like,vortex-like orderly arrangement,resembling fibroblasts;after 10 passages,the irregular morphology of the ADSCs and decreased proliferation rate were found.The isolated ADSCs showed potential for the osteogenic and adipogenic differentiation,and the expressions of CD29 and CD44 proteins were positive.The transmission electron microscope observation resuls showed that the ADSC-Exos appeared disc-shaped,and the main peak of particle size distribution was around 132 nm.The CD9 and TSG101 proteins were positively expressed in the ADSC-Exos,indicating successful extraction.The fluorescence microscope results showed red fluorescence signals around the nuclei of the RAW264.7 cells,indicating the uptake of ADSC-Exos by the macrophages.Compared with control group,the rates of EdU positive cells in 10,20,and 40 mg·L-1 ADSC-Exos groups were significantly increased(P<0.05);compared with 10 mg·L-1 ADSC-Exos group,the rate of EdU positive cells in 20 mg·L-1 ADSC-Exos group was significantly increased(P<0.05).Compared with control group,the numbers of migration cells in 10,20,and 40 mg·L-1 ADSC-Exos groups were significantly increased(P<0.05);compared with 10 mg·L-1 ADSC-Exos group,the numbers of migration cells in 20 and 40 mg·L-1 ADSC-Exos groups were significantly increased(P<0.05).Compared with control group,the numbers of the adherent macrophages in 10,20,and 40 mg·L-1 ADSC-Exos groups were significantly increased(P<0.05);compared with 10 mg·L-1 ADSC-Exos group,the number of adherent macrophages in 20 mg·L-1 ADSC-Exos group was significantly increased(P<0.05).Conclusion:The ADSC-Exos can be internalized by the macrophages and they can enhance the migration ability of the macrophages by affecting the cell adhesion.

Objective To investigate the role of nucleotide-binding oligomerization domain 2(NOD2)modified by palmitoyltransferase(ZDHHC5)in brain injury after cardiopulmonary resuscitation(CPR)in mice.Methods Twenty-four male C57BL/6J mice were divided into the blank group,the control group,the ZDHHC5-si group and the NOD2-si group,with 6 mice in each group.Except for the blank group without any treatment,CPR modeling was performed in the other three groups.At 24 h before CPR,mice in the ZDHHC5-si group and the NOD2-si group were injected with ZDHHC5 siRNA and NOD2 siRNA via tail vein,respectively.The modified neurological deficit scale(mNSS)was used to evaluate the neurological function at 24 h,48 h and 72 h in each group.Blood samples and brain tissue were collected 72 h after modeling.Real-time fluorescent quantitative PCR(qPCR)was used to detect ZDHHC5 and NOD2 in brain tissue.The protein expression levels of IL-1β,TNF-α and IL-6 in plasma were detected by enzyme-linked immunosorbent assay(ELISA).Colorimetric method and thiobarbituric acid(TBA)method were used to detect protein expression levels of MDA and MPO in brain tissue,respectively.Western blot assay was used to detect expression levels of Cleaved Caspase-3,ZDHHC5 and NOD2 in brain tissue.HE pathological sections of brain tissue were observed under light microscope.The pathological sections of brain tissue were observed by TUNEL under fluorescence microscope.Results Compared with the blank group,the mNSS score,the expression levels of IL-1β,TNF-α,IL-6,MDA and MPO,and the protein expression levels of Cleaved Caspase-3,ZDHHC5 and NOD2 were significantly increased(P＜0.05),and brain tissue damage and cell apoptosis were aggravated in the other three groups.Compared with the control group,the above indicators were significantly decreased in the ZDHHC5-si group and the NOD2-si group(P＜0.05),and brain tissue damage and cell apoptosis were significantly attenuated.Compared with the NOD2-si group,the above parameters were significantly decreased(P＜0.05),and brain tissue damage and cell apoptosis were further attenuated in the ZDHHC5-si group.Conclusion In the mouse CPR model,NOD2 can produce palmitoylated NOD2 after regulated by ZDHHC5,which further promotes the release of inflammatory factors and causes neuronal apoptosis,ultimately damaging brain tissue and affecting neurological function.