Periodontal disease is a risk factor for many systemic diseases such as Alzheimer's disease and adverse pregnancy outcomes. Cleft palate (CP), the most common congenital craniofacial defect, has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection. A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring. However, the precise relationship remains unclear. In this study, the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P. gingivalis injected intravenously and orally into pregnant mice. We investigated an obvious increasing CP (12.5%) in sonicated P. gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium. Then glycolysis and H4K12 lactylation (H4K12la) were detected to elevate in both mouse embryonic palatal mesenchyme (MEPM) cells and macrophages under P. gingivalis exposure which further promoted the transcription of metallopeptidase domain17 (ADAM17), subsequently mediated the shedding of transforming growth factor-beta receptor 1 (TGFBR1) in MEPM cells and mer tyrosine kinase (MerTK) in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate, eventually caused abnormalities in palate fusion and ossification. The abnormal efferocytosis also led to a predominance of M1 macrophages, which indirectly inhibited palatal osteogenesis via extracellular vesicles. Furthermore, pharmacological ADAM17 inhibition could ameliorate the abnormality of P. gingivalis-induced abnormal palate development. Therefore, our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.
Animals ; Female ; Porphyromonas gingivalis ; Pregnancy ; Mice ; Cleft Palate/etiology* ; Glycolysis

Objective:To analyze the impact of DRG payment method reform on hospitalization costs and structure in traditional Chinese medicine hospitals.Methods:Using the cost data of hospitalized patients from 2017 to 2022 for public traditional Chinese medicine hospitals in Qingyang and Tianshui,descriptive statistics and two groups interrupted time-series models were implemented to compare the changes before and after DRG payment method reform.Results:DRG payment method reform had no effective impact on the secondary traditional Chinese medicine hospital's average hospitalization costs,average Chinese medicine costs,and average western medicine costs(P＞0.05),but the average proportion of western medicine costs showed an obvious downward trend after the reform(β9=-0.19,P＜0.01).DRG payment method reform resulted in tertiary traditional Chinese medicine hospitals turning to obvious decreasing trends in average hospitalization costs,average Chinese medicine costs,and average western medicine costs(P＜0.05),while the pre-reform decreasing trends in the average proportion Chinese medicine costs share of both secondary and tertiary traditional Chinese medicine hospitals were curbed in the post-reform period.Conclusion:DRG payment method reform had effectively controlled hospitalization costs,Chinese medicine costs,and western medicine costs of tertiary traditional Chinese medicine hospitals,while the cost control of secondary traditional Chinese medicine hospitals has been ineffective,probably contributing to the enhancement of the use of Chinese medicine and the average proportion of Chinese medicine costs.DRG payment method reform for Chinese medicine should strengthen the supervision of costs,actively utilize the advantages of the characteristics of Chinese medicine,and promote the differentiated reform of traditional Chinese medicine hospitals.

Objective To investigate the biomechanical characteristics of the mandibular anterior teeth intrusion assisted by buccal mini-implants,so as to provide theoretical guidance for the clinical treatment of deep overbite and other conditions requiring intrusion of the mandibular anterior teeth.Methods A finite element model of implant screws,clear aligners(CAs)and mandibular complex including the mandibular dentition,periodontal ligament(PDL)and alveolar bone was constructed.The model was designed with 0.2 mm intrusion in the mandibular anterior teeth.Seven groups were set:without traction,30 g,50 g,100 g,150 g,200 g,and 250 g force groups.The stress and displacement of the teeth as well as the related stress distributions of PDL and CAs in each group after loading were analyzed.Results Without traction and under different traction forces,the mandibular anterior teeth tended to be tipped and intruded.With the increase of traction force,the increasing trend was manifested in the vertical displacement and labial displacement of the mandibular anterior teeth.When the traction force reached 200 g,the vertical displacement showed a significant increase,the subsequent increase then showed a tendency to flatten.The ratio of the labial tipping displacement to the intrusive displacement of the mandibular anterior teeth showed a decreasing trend with the increase of traction force.Within a reasonable force range,increasing traction force led to greater bodily intrusion of the anterior teeth.When the traction force was less than 150 g,the mandibular posterior teeth exhibited a tendency of extrusion.When the traction force of more than 150 g was applied,it showed a tendency of intrusion.The PDL stress was concentrated on the labial and cervical surface of the anterior teeth.Conclusions Intrusion efficiency of the mandibular anterior teeth has been effectively improved with CAs assisted by buccal mini-implants.Moreover,the traction force of the mini-implants has a significant impact on the movement of the mandibular anterior teeth.Based on a comprehensive analysis of factors such as the displacement trend of the mandibular dentition and the PDL stress,the optimal force value for buccal traction of the mini-implants to intrude the mandibular anterior teeth can be selected as 150-200 g force.

Objective To measure the policy synergy of the"Three Medical"policies in Traditional Chinese Medicine across 7 national TCM Comprehensive Reform Pilot Zones,providing a scientific basis for policy optimization.Methods Utilizing text mining techniques to explore the focus of the"Three Medical"policies in 80 TCM comprehensive reform construction plans,and employing the PMC index model to evaluate their vertical policy synergy,while using the coupling synergy model to measure their horizontal synergy.Results The overall policy synergy of the"Three Medical"policies in the sample regions has a mean value of 0.52.Specifically,the policy synergy between TCM healthcare and herbal medicine policies has a mean value of 0.60,between TCM healthcare and health insurance policies has a mean value of 0.57,and between herbal medicine and health insurance policies has a mean value of 0.47.The mean policy difference between provinces and cities in the sample regions is 0.023,and between cities and counties is 0.010.Conclusion The"Three Medical"policies in the sample regions are in a state of reluctant synergy.Among the"Three Medical"system,the policy synergy is highest between TCM healthcare and herbal medicine,followed by TCM healthcare and health insurance,with the lowest being between herbal medicine and health insurance.Additionally,the policy synergy between"Three Medical"policies at the city-county level is higher than at the province-city level.There is a continued need to optimize the horizontal and vertical policy synergy of policies at different levels within the comprehensive reform policies of TCM in the TCM Comprehensive Reform Pilot Zones.

Objective To quantitatively evaluate the synergy level of Traditional Chinese Medicine(TCM)"three-medical"and advance TCM revitalization and healthcare reform.Methods Sort out the quantitative evalution indictors of the"three-medical"in TCM based on policy texts.Policy-derived evaluation indicators were refined through the Delphi method.The composite system synergy degree model was applied to calculate subsystem order degrees and overall synergy degrees across seven national TCM reform demonstration zones.Results From 2021 to 2023:the mean value of the orderliness of the TCM medical system in the 7 demonstration areas increased from 0.31 to 0.72,the orderliness of the TCM health insurance increased from 0.23 to 0.74,and the orderliness of the Herbal System increased from 0.34 to 0.70.From 2022 to 2023,the average value of synergy between medical and health insurance systems in the field of Chinese medicine in 7 demonstration areas grew from 0.17 to 0.29.The synergy between medical and pharmaceutical systems in the field of Chinese medicine grows from 0.19 to 0.31.The synergy between pharmaceutical and health insurance system in the field of Chinese medicine increased from 0.17 to 0.27.The overall synergy of the"three-medical"system of TCM increased from 0.19 to 0.36.Conclusion The degree of orderliness of the"three-medical"systems of TCM is gradually rising,showing a relatively good development trend in orderliness.The degree of synergy among the"three-medical"total systems of TCM is on the rise,but is still at the level of moderate synergy or below.

Antibody humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic antibodies originated from animal models.Computational suggestions have long been desired,but available tools focused on immunogenicity calculation of whole antibody sequences and sequence segments,missing the individual residue sites.This study introduces Site-specific Immunogenicity for Therapeutic Antibody(SITA),a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody,but also individual residues,based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures.A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Antibody-Antibody structural complexes.On an independent testing dataset derived from 13 Antibody-Antibody structural complexes,SITA successfully predicted the epitope sites for Antibody-Antibody structures with a receiver operating characteristic(ROC)-area unver the ROC curve(AUC)of 0.85 and a precision-recall(PR)-AUC of 0.305 at the residue level.Furthermore,the SITA score can significantly distinguish immunogenicity levels of whole human antibodies,therapeutic antibodies and non-human-derived antibodies.More importantly,analysis of an additional 25 thera-peutic antibodies revealed that over 70％of them were detected with decreased immunogenicity after modification compared to their parent variants.Among these,nearly 66％antibodies successfully iden-tified actual modification sites from the top five sites with the highest SITA scores,suggesting the ability of SITA scores for guide the humanization of antibody.Overall,these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

Objective: To investigate the association between emotional intelligence and sleep problems at the symptom level among junior and senior high school students, so as to provide new insights for interventions targeting junior and senior high school students sleep disorders. Methods: From November 2023 to May 2024, a stratified cluster random sampling method was employed to select 3 531 first year junior high school and first year senior high school students from 6 schools in Guangyuan City and Liangshan Yi Autonomous Prefecture in Sichuan Province, as well as Lhasa City in Tibet Autonomous Region. The Insomnia Severity Index Scale and the Wong and Law Emotional Intelligence Scale(WLEIS) were used to assess sleep problems and emotional intelligence. A network analysis was performed to explore the relationship between emotional intelligence and sleep disorders, and a gender based network comparison analysis was conducted. Results: The reported rate of sleep problems among junior and senior high school students was 47.3%, with severe sleep problems of 2.2%. Difficulty maintaining sleep, worry about sleep, and emotional application were the core symptoms in the network (node strength values: 1.11, 0.98, and 0.82, respectively). Dissatisfaction with sleep and emotional application served as bridge symptoms connecting emotional intelligence and sleep problems (bridge strength values: 1.77 and 1.59, respectively). The edge weights of the emotional intelligence and sleep problems network differed significantly between genders (maximum difference in edge weight values was 0.13， P <0.05). Conclusions Emotional application ability and dissatisfaction with sleep are the key nodes in the network connecting emotional intelligence and sleep problems. Targeted efforts to enhance emotional application ability may effectively reduce the risk of sleep problems among junior and senior high school students.

Antibody (Ab) humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic Abs originated from animal models. Computational suggestions have long been desired, but available tools focused on immunogenicity calculation of whole Ab sequences and sequence segments, missing the individual residue sites. This study introduces Site-specific Immunogenicity for Therapeutic Antibody (SITA), a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody, but also individual residues, based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures. A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Ab-Ab structural complexes. On an independent testing dataset derived from 13 Ab-Ab structural complexes, SITA successfully predicted the epitope sites for Ab-Ab structures with a receiver operating characteristic (ROC)-area unver the ROC curve (AUC) of 0.85 and a precision-recall (PR)-AUC of 0.305 at the residue level. Furthermore, the SITA score can significantly distinguish immunogenicity levels of whole human Abs, therapeutic Abs and non-human-derived Abs. More importantly, analysis of an additional 25 therapeutic Abs revealed that over 70% of them were detected with decreased immunogenicity after modification compared to their parent variants. Among these, nearly 66% Abs successfully identified actual modification sites from the top five sites with the highest SITA scores, suggesting the ability of SITA scores for guide the humanization of antibody. Overall, these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

Objective To investigate the effects of integrating pelvic floor magnetic stimulation and medium-frequency pulsed electrotherapy with biofeedback on alleviating obstructed defecation symptoms in patients diagnosed with pelvic floor spasm syndrome.Methods A total of 133 patients diagnosed with pelvic floor spasm syndrome at the Gastrointestinal Surgery Outpatient and Inpatient Departments of the Third Hospital of Hebei Medical University between January 2017 and January 2025 were enrolled in this study.All patients underwent two sessions of conventional biofeedback therapy.According to the additional treatments they received,the patients were catego-rized into four groups:the Control group(received biofeedback therapy only);the Magnetic Stimulation group(received two additional sessions of pelvic floor magnetic stimulation);the Electrical Stimulation group(received two additional sessions of medium-frequency pulse electrical therapy);and the Magnetic-Electric Combined group(received two additional sessions of both pelvic floor magnetic stimulation and medium-frequency pulse electrical therapy).The improvement in obstructed defecation symptoms was evaluated before treatment,after treatment,and at the 3-month follow-up across all four groups.Results A total of 133 patients diagnosed with pelvic floor spasm syndrome were enrolled in this study.After a 3-month follow-up period,8 patients were lost to follow-up(6.0%).Consequently,125 patients completed the follow-up and were included in the final analysis.These patients were distributed across four groups:the control group(n=32),the magnetic stimulation group(n=30),the electrical stimulation group(n=31),and the combined magneto-electric stimulation group(n=32).Compared with biofeedback therapy alone,combination therapy led to a greater reduction in the need for manual assistance during defecation,the sensation of incomplete evacuation,and the requirement for straining during defecation,with the most pronounced improvements observed in the combined magneto-electric stimulation group.Conclusions The integration of biofeedback,pelvic floor magnetic stimulation,and medium-frequency pulse electrotherapy can significantly alleviate symptoms including straining during defecation,the sensation of incomplete bowel evacua-tion,and reduce the need for manual assistance.Moreover,this combined approach contributes to the stabilization and maintenance of therapeutic effects in the short term.

Objective:It aims to examine the effects of the employee medical insurance outpatient mutual assistance on medical insurance costs for patients with diabetes mellitus,offering insights for optimizing outpatient insurance policies and chronic disease management strategies.Methods:Outpatient cost settlement data of urban employees with diabetes mellitus in Lanzhou from 2022 to 2023 was collected.Univariate analysis and interrupted time-series models were used to compare relevant medical insurance cost indicators before and after the reform.Results:The inpatient data of 765 730 diabetes mellitus patients were included in the study,and male patients account for 62.67％.After the reform,average per-visit pooling fund expenditure,average per-visit individual payment expenditures,average per-visit personal account expenditure,average per-visit eligible expense amount,average per-visit total fund payment,and the average per-visit proportion of basic medical pooling payments were decreased(P＜0.05).Moreover,average per-visit pooling fund expenditure,average per-visit individual account expenditure,average per-visit cash payment,average per-visit eligible expense amount,average per-visit total fund payment,and the average per-visit proportion of basic medical pooling payments showed a notable declining trend post-reform(P＜0.05).In contrast,the per-visit fully out-of-pocket expenditure exhibited no significant change before and after the reform(P＞0.05).Conclusion:The reform of the employee medical insurance outpatient mutual assistance system has alleviated the economic burden of disease for diabetic patients and improved the efficiency of medical insurance fund utilization,but it reduced the proportion of basic medical pooling payments.It is recommended to continuously refine the outpatient medical insurance payment system,strengthen supervision of medical expenses and service quality,and balance patient benefits with fund pressure to enhance chronic disease outpatient benefits.