Background and aims As a ferroptosis inducer, sorafenib, a first-line treatment for hepatocellular carcinoma (HCC), has a significant antitumor effect. Nonetheless, HCC patients frequently develop sorafenib resistance. Here, we investigated the impacts of progestagen-associated endometrial protein (PAEP), which controls sorafenib resistance and tumorigenesis in HCC. Furthermore, we investigated the function of PAEP and the underlying molecular mechanisms that cause HCC ferroptosis when sorafenib is applied. Methods Western blot analysis, cell proliferation, colony formation and animal experiments were performed to investigate the function of PAEP in sorafenib resistance and tumorigenesis in HCC. We detected the levels of reactive oxygen species, iron, and malondialdehyde and preformed transmission electron microscopy to investigate the relationship between PAEP and ferroptosis. Co-immunoprecipitation (co-IP) assay was performed to investigate the underlying molecular mechanisms of PAEP that cause HCC ferroptosis. Results PAEP was significantly overexpressed in HCC tissues, and this was associated with a poor clinical prognosis. PAEP silencing dramatically reduced HCC cells’ malignant phenotype. We found that sorafenib-induced ferroptosis was more sensitive to HCC cells with PAEP knockdown. Furthermore, the orthotopic cell line-derived xenograft mouse model results showed that sorafenib sensitivity can be effectively increased in vivo by PAEP knockdown. We determined that transferrin (TF) was a PAEP target using the String database, and we further supported this finding with Co-IP analysis. Additionally, on sorafenib-induced ferroptosis in HCC cells, TF partially reversed the effects of PAEP knockdown. Conclusions Our research indicates that PAEP may be a potential biomarker for predicting sorafenib resistance in HCC and disruption of PAEP expression may be a potential cancer-directed therapeutic option for HCC.

Objective: To explore the association between executive function and emotional and behavioral problems in first-grade elementary school students, so as to provide a reference for promoting children s mental health. Methods: From March to May 2024, 423 first-grade elementary school students from 6 primary schools aged 6-7 were selected by using stratified cluster random sampling in Shanxi, Shanghai, Shandong, Guangxi, Xinjiang, and Jiangxi. Data were collected by using the Executive Function Assessment Scale and the Strengths and Difficulties Questionnaire. An independent samples t-test was used to analyze differences in executive function of different genders and differences in emotional and behavioral problems among first-grade school students with varying executive function levels; a linear regression model was employed to analyze the association between children s executive function and emotional and behavioral problems. Results: A total of 42 first-grade elementary school students (9.9%) were identified as having executive function deficits. Students in the executive function deficit group scored higher on internalizing behavior (7.50±0.52), externalizing behavior (11.26±0.52), and total difficulties (18.52± 0.93 ) were significantly higher than those of children without deficits (4.37±0.14, 6.69±0.17, 10.64±0.27) ( t =5.79, 8.50, 9.23, all P <0.05). Results of linear regression analysis showed that, after controlling for relevant covariates such as gender, age, family economic status, being an only child, and body mass index, the factor scores, dimensional scores, and total scores of executive function were all positively correlated with scores for externalizing problems, internalizing problems, and total difficulties ( β =0.07-0.32, all P <0.05). Conclusions Children s executive function is closely associated with emotional and behavioral problems, and those with poorer executive function exhibit more pronounced emotional and behavioral problems. Improving children s executive function may help promote their mental health.

Objective: To investigate the relationship between night-time noise exposure and depressive symptoms among junior and senior high school students, so as to provide evidence to support strategies for promoting their physical and mental health. Methods: From September 2024 to December 2025, 2 900 junior and senior high school students were selected using stratified cluster random sampling in the three cities of Nanning, Lhasa, and Yanji. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess depressive symptoms in junior and senior high school students, and a noise exposure survey was conducted. Chi-square test was used to compare the prevalence of depressive symptoms among junior and senior high school students with different types of night-time noise exposure, and Logistic regression models were employed to examine the association between night-time noise exposure and depressive symptoms among junior and senior high school students. Results: The prevalence of depressive symptoms among junior and senior high school students without night-time noise exposure was 33.0%, while that among junior and senior high school students with night-time noise exposure was 49.0%; the difference was statistically significant ( χ 2= 45.85 , P <0.01) . After adjusting for gender, age and region, Logistic regression analysis showed that exposure to night-time traffic noise, neighborhood noise, air conditioner noise, and other types of noise showed increased risk of detecting depressive symptoms in junior and senior high school students ( OR =2.22, 1.84, 2.41, 2.17, all P <0.05). Conclusion Night-time noise exposure is associated with an increased risk of depressive symptoms among junior and senior high school students.

Abstract Children s emotional and behavioral problems are characterized by a relatively high incidence, concealed manifestations, and a potential correlation with an increased risk of subsequent mental disorders. These problems have a sustained impact on children s social-emotional development, learning adaptation, and peer relationships. The study reviews the main influencing factors and their mechanisms of action regarding children s emotional and behavioral problems from three levels:individual, family, and social. Under a multi-level integrated perspective, it deepens the understanding of these mechanisms and proposes that future efforts should focus on factors such as improving physical fitness, enhancing sleep, and reducing sedentary behavior. Furthermore, it suggests strengthening collaborative interventions among schools, families, and communities to promote the early prevention of childrens emotional and behavioral problems and support their healthy development.

Objective: To summarize the best evidence for the management of patients with gastrointestinal graft-versushost disease after hematopoietic stem cell transplantation, and provide evidence-based references for clinical nursing work. Methods: A systematic search was conducted for relevant evidence on the management of patients with gastrointestinal graft-versus-host disease after hematopoietic stem cell transplantation from domestic and foreign databases, as well as websites of blood and bone marrow transplantation related societies. The search period was from the establishment of the database until February 2026. Results: After screening, a total of 19 articles were included, encompassing 3 clinical decisions, 1 recommended practice, 4 guidelines, 7 expert consensuses, and 4 evidence summaries. Twenty-five pieces of best evidence were summarized across 8 aspects: multidisciplinary collaboration, influencing factors, assessment and monitoring, diagnostic differentiation, symptom management, dietary nutrition, medication guidance, and health education. Conclusion: Summarizing the relevant evidence on the management of patients with gastrointestinal graft-versus-host disease after hematopoietic stem cell transplantation can provide evidence-based support for clinical medical staff, and it is recommended to apply it in combination with clinical practice and patient wishes.

Objective To explore the characteristics and molecular mechanisms of dynamic changes in ovarian function during natural aging in mice.Methods Eighteen female ICR mice of 2,6,10 and 14 months of age(referred to as 2 M,6 M,10 M,and 14 M)were included.The estrous cycle,ovarian index,pregnancy rate and embryo number were detected.The number of follicles was observed using HE staining.Serum anti-Müllerian hormone(AMH)levels were measured using ELISA.Protein and mRNA expression of P16,P21,proliferator-activated receptor-γ coactivator-1α(PGC-1α),and mitochondrial transcription factor A(TFAM)were detected through IHC and qPCR,respectively,and the protein expression of PGC-1α and TFAM was detected by Western blot.Relationships between indicators were evaluated based on Spearman's rank correlation coefficients and logistic regression analyses.Results Compared with estimates in the 2 M group,the percentage of estrous cycle disorders(P＜0.05 in 10 M group,P＜0.01 in 14 M group),ovarian index(P＜0.05 in 10 M group,P＜0.01 in 14 M group),serum AMH level(P＜0.01 in 10 M group,P＜0.01 in 14 M group),number of embryos(P＜0.01 in the 10 M group,P＜0.01 in 14 M group),and pregnancy rate(P＜0.01 in 14 M group)were significantly lower;the number of follicles at all levels and total number of follicles were lower(all P＜0.01),and the number of atretic follicles(all P＜0.01)was higher.Furthermore,P16 and P21 mRNA(P16:P＜0.01 in 10 M and 14 M groups;P21:P＜0.05 in 10 M group,P＜0.01 in 14 M group)and protein levels(P16:P＜0.01 in each group;P21:P＜0.01 in 10 M and 14 M groups)were elevated.Spearman's correlation analyses showed that the age in months was negatively correlated with the ovarian index,serum AMH level,primordial follicle number,number of embryos,and expression of PGC-1αand TFAM and positively correlated with the expression of atretic follicle,P16 and P21(all P＜0.01).Logistic regression analysis revealed a significant negative correlation between the age in months and pregnancy rate(P＜0.01).PGC-1α mRNA was significantly decreased(all P＜0.01),and TFAM mRNA was significantly decreased in 10 M and 14 M groups(P＜0.01).PGC-1α levels were significantly decreased in the 10 M group(IHC:P＜0.05;Western blot:P＜0.01)and 14 M group(all P＜0.01);TFAM levels were significantly lower in 6 M,10 M,and 14 M groups than in the 2 M group(IHC:P＜0.01;Western blot:P＜0.01).Compared with the 2 M group,expression levels of PGC-1α and TFAM were positively correlated with the ovarian index and serum AMH level and negatively correlated with P16 and P21 expression(all P＜0.01).Conclusions Ovarian function in mice declines progressively with age in months,as reflected by reductions in follicles and fertility and the up-regulation of aging markers,which may be associated with the decreased expression of the mitochondrial biogenesis factors PGC-1α and TFAM.

Objective:To investigate the effect of the sizes of osteon-like concentric microgroove structures on the osteoclastic differentiation of macrophages on titanium surfaces, and to provide reference for the surface modification of implants.Methods:The silicon wafers sputtered with titanium were selected as the control group (smooth surface specimens) and four concentric groups (concentric circles with the maximum diameter of 200 μm, the minimum diameter of 20 μ m, the spacing of concentric circles of 10 or 30 μm, the width of microgrooves of 10 or 30 μm, and the depth of microgrooves of 5 or 10 μm) specimens (the total sample size in each group was 27). The width of microgrooves of C10-5 and C10-10 groups was 10 μm, the depth was 5 and 10 μm, and the width of microgrooves of C30-5 and C30-10 groups was 30 μ m, the depth was 5 and 10 μ m, respectively. The physicochemical properties of the material surfaces were characterized using scanning electron microscopy and contact-angle measurement. The proliferation, adhesion of macrophage-like cell line RAW264.7 and the formation of osteoclast actin-rings on the specimen surfaces were observed by cell counting kit-8 (CCK-8), immunofluorescence staining and laser confocal microscopy. Tartrate resistant acid phosphatase (TRAP) quantitative detection, real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting were used to investigate the regulation of osteon-like concentric microgroove structures on the specimen surfaces on the osteoclastic differentiation of macrophages.Results:Macrophages aggregated and grew disorderly on the surface of the smooth group, and arranged in concentric circles along the microgroove structures on the surfaces of the concentric groups. After 5 days of culture, the cell proliferation of C30 groups (the A values of C30-5 group and C30-10 group were 1.335±0.018 and 1.340±0.033, respectively) was significantly higher than that of C10 groups (the A values of C10-5 group and C10-10 group were 0.967±0.015 and 1.182±0.020, respectively)(all P<0.05). The cell proliferation of the four concentric groups was significantly higher than that of the control group (the A value was 0.796±0.012), with statistical significance (all P<0.05). After osteoclastic induction for 5 days the osteoclasts induced in the C10-5 and C10-10 groups exhibited smaller actin rings and fewer numbers. The TRAP activity in each concentric group was significantly lower than that in the control group ( P<0.05). The expression levels of osteoclast differentiation-related genes TRAP (0.610±0.022) in the C10-10 group was lowest, and CtsK (0.489±0.136, 0.445±0.037) in the C10-5 and C10-10 groups were lower compared to the smooth group and other concentric groups, with statistical significance (all P<0.05), the expression levels of osteoclast differentiation-related proteins TRAP (0.648±0.041), MMP-9 (0.688±0.026) in the C10-10 group were lowest, and CtsK (0.491±0.016, 0.453±0.010) in the C10-10 and C30-10 groups were also lower compared to the smooth group and other concentric groups, with statistical significance (all P<0.05). Conclusions:The osteon-like concentric microgroove structures inhibit the osteoclastic differentiation of macrophage-like cell line RAW264.7, with the microgrooves 10 μm wide and 10 μm deep showing the most significant inhibitory effect on the osteoclastic differentiation.

Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways. Increasing evidence suggests that imbalances in central nervous system function play an essential role in the progression of visceral pain, but the exact mechanisms underlying the neural circuitry and molecular targets remain largely unexplored. In the present study, the ventral tegmental area (VTA) was shown to mediate visceral pain in mice. Visceral pain stimulation increased c-Fos expression and Ca²⁺ activity of glutamatergic VTA neurons, and optogenetic modulation of glutamatergic VTA neurons altered visceral pain. In particular, the upregulation of NMDA receptor 2A (NR2A) subunits within the VTA resulted in visceral pain in mice. Administration of a selective NR2A inhibitor decreased the number of visceral pain-induced c-Fos positive neurons and attenuated visceral pain. Pharmacology combined with chemogenetics further demonstrated that glutamatergic VTA neurons regulated visceral pain behaviors based on NR2A. In summary, our findings demonstrated that the upregulation of NR2A in glutamatergic VTA neurons plays a critical role in visceral pain. These insights provide a foundation for further comprehension of the neural circuits and molecular targets involved in chronic visceral pain and may pave the way for targeted therapies in chronic visceral pain.
Animals ; Male ; Visceral Pain/metabolism* ; Up-Regulation/physiology* ; Ventral Tegmental Area/metabolism* ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; Neurons/drug effects* ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Chronic Pain/metabolism* ; Glutamic Acid/metabolism*

Patients with periodontal disease often require combined periodontal-orthodontic interventions to restore periodontal health, function, and aesthetics, ensuring both patient satisfaction and long-term stability. Managing these patients involving orthodontic tooth movement can be particularly challenging due to compromised periodontal soft and hard tissues, especially in severe cases. Therefore, close collaboration between orthodontists and periodontists for comprehensive diagnosis and sequential treatment, along with diligent patient compliance throughout the entire process, is crucial for achieving favorable treatment outcomes. Moreover, long-term orthodontic retention and periodontal follow-up are essential to sustain treatment success. This expert consensus, informed by the latest clinical research and practical experience, addresses clinical considerations for orthodontic treatment of periodontal patients, delineating indications, objectives, procedures, and principles with the aim of providing clear and practical guidance for clinical practitioners.
Humans ; Consensus ; Orthodontics, Corrective/standards* ; Periodontal Diseases/complications* ; Tooth Movement Techniques/methods* ; Practice Guidelines as Topic

Diabetic retinopathy, a prevalent and vision-threatening microvascular complication of diabetes mellitus, is the leading cause of blindness among middle-aged and elderly individuals. Natural diterpenoids isolated from Siegesbeckia pubescens demonstrate potent anti-inflammatory properties. This study aimed to identify novel bioactive diterpenoids from S. pubescens and investigate their effects on oxidative stress and inflammatory responses in diabetic retinopathy, both in vitro and in vivo. Three new ent-pimarane-type diterpenoids (1-3) and six known compounds (4-9) were isolated from the aerial parts of S. pubescens. Their structures were elucidated through spectroscopic data interpretation, and absolute configurations were determined by comparing calculated and experimental electronic circular dichroism (ECD) spectra. Among these compounds, 14β,16-epoxy-ent-3β,15α,19-trihydroxypimar-7-ene (5) exhibited the most potent protective effect against high glucose and interleukin-1β (IL-1β)-stimulated human retinal endothelial cells. Mechanistically, compound 5 promoted endothelial cell survival while ameliorating oxidative stress and inflammatory response in diabetic retinopathy, both in vivo and in vitro. These findings not only suggest that diterpenoids such as compound 5 are important anti-inflammatory constituents in S. pubescens, but also indicate that compound 5 may serve as a lead compound for preventing or treating vascular complications associated with diabetic retinopathy.
Diabetic Retinopathy/metabolism* ; Humans ; Oxidative Stress/drug effects* ; Animals ; Diterpenes, Kaurane/administration & dosage* ; Asteraceae/chemistry* ; Male ; Endothelial Cells/drug effects* ; Abietanes/administration & dosage* ; Molecular Structure ; Mice ; Anti-Inflammatory Agents/chemistry* ; Plant Extracts/chemistry* ; Mice, Inbred C57BL