Alzheimer's disease (AD) remains a formidable challenge in modern healthcare, necessitating innovative approaches for its early detection and intervention. This study aimed to enhance the identification of individuals with mild cognitive impairment (MCI) at risk of developing AD. Leveraging advances in computational power and the extensive availability of healthcare data, we explored the potential of deep learning models for early prediction using medical claims data. We employed a bidirectional gated recurrent unit (BiGRU) deep learning model for predictive modeling of MCI progression across various prediction intervals, extending up to five years post-initial MCI diagnosis. The performance of the BiGRU model was rigorously compared with several machine-learning model baselines to evaluate its efficacy. Using a robust cross-validation methodology, the BiGRU emerged as the top-performing model, achieving an Area Under the Receiver Operating Characteristic Curve (AUC-ROC) of 0.833 (95% CI: 0.822, 0.843), an Area Under the Precision-Recall Curve (AUC-PR) of 0.856 (95% CI: 0.845, 0.867), and an F1-Score of 0.71 (95% CI: 0.694, 0.724) for a five-year prediction interval. The results indicate that BiGRU, utilizing longitudinal claims data, reliably predicts MCI-to-AD progression over a lengthy interval following the initial MCI diagnosis, offering clinicians a valuable tool for targeted risk identification and stratification.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Sepsis, a life-threatening organ dysfunction caused by an abnormal host response to infection, remains one of the leading causes of mortality in critically ill patients, but there is currently a lack of effective early warning systems and therapeutic strategies for sepsis. In recent years, the interaction between the nervous and immune systems has gained considerable attention. However, the precise mechanisms underlying sepsis-related organ damage and the complex interplay among different organs remain poorly understood. The inflammatory reflex, which involves the central nervous system integrating incoming inflammatory signals and reflexively modulating peripheral inflammatory responses, is a critical interface where the central nervous network regulates peripheral immunity. Modulating the inflammatory reflex to correct immune dysfunction may represent a promising therapeutic breakthrough for sepsis. Nevertheless, the precise mechanisms by which the inflammatory reflex induces changes in both the central nervous system and the peripheral immune system in sepsis, as well as its role in organ damage, remain to be elucidated. To this end, the authors reviewed the researches on the role of the inflammatory reflex in the development and progression of sepsis-related organ damage, aiming to provide novel insights into more effective therapeutic strategies for sepsis.

Objective To investigate the current situation of frailty in patients with home peritoneal dialysis and analyze its influencing factors,so as to provide bases for early identification of high-risk groups and targeted clinical intervention.Methods From October to December 2024,205 home-based peritoneal dialysis patients under long-term follow-up at a tertiary A hospital in Zhongshan,Guangdong Province,were selected by convenience sampling.The General Information Questionnaire,Fried Phenotype Scale,Nutritional Risk Screening Tool,Exercise Self-Efficacy Scale,and Social Support Rating Scale were used to investigate the influencing factors of frailty in home-based peritoneal dialysis patients by ordinal logistic regression analysis.Results A total of 201 valid questionnaires were collected.The prevalence of frailty among home-based peritoneal dialysis patients was 24.3％,while 39.3％were in the pre-frailty stage,and 36.3％showed no frailty.0rdinal logistic regression analysis revealed that age,residence location,primary disease,sleep status,serum albumin concentration,and exercise self-efficacy level were influencing factors of frailty in the home peritoneal dialysis patients(P＜0.05).Conclusion The incidence of frailty in patients with home peritoneal dialysis is higher,and patients with advanced age,living in rural areas,other types of primary diseases,insomnia,low serum albumin concentration and low exercise self-efficacy are more likely to develop frailty.Specialist doctors and nurses of peritoneal dialysis should pay attention to the early screening of frailty in patients with peritoneal dialysis at home,and take personalized intervention measures to prevent or delay the occurrence of frailty according to the relevant risk factors.

Objective:To explore the distribution characteristics of glioma-associated oncogene homolog 1 (Gli1) positive cells during orthodontic tooth movement process and conduct a proteomic analysis of these cells.Methods:Forty Gli1-LacZ transgenic mice were used to establish an in vivo orthodontic tooth movement (OTM) model for labeling Gli1 positive cells in Gli1-LacZ transgenic mice (OTM group) and an unforced control group, with tooth movement distance measured using micro-CT. The spatial relationship and distribution characteristics of Gli1 positive cells and H-type vessels of CD31 and endomucin (EMCN) in periodontal tissues were detected by immunofluorescence staining. Twenty Gli1-membrane-targeted tandem dimer Tomato (mT)/membrane-targeted green fluorescent protein (mG) double-genotype mice were bred and Gli1 positive cells were sorted for proteomic sequencing after tamoxifen induction. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used for enrichment analysis. Results:The micro-CT three-dimensional reconstruction results showed that the mesial movement of the maxillary first molar in mice after 7 days of force application was (69±15) μm, indicating the successful establishment of the Gli1-LacZ transgenic mouse OTM model. Immunofluorescence staining showed that the blood vessels in periodontal tissue were mostly H-type vessels of CD31 and EMCN. The blood vessels in the periodontal tissues are predominantly H-type vessels positive for both CD31 and EMCN. The percentage of Gli1 positive cells in the OTM group, expressed as (54.5±13.2)%, and the relative fluorescence intensity, expressed as 2.6±0.9, were both significantly greater than those in the control group, which had a Gli1 positive cell percentage of (36.3±9.1)% ( t=3.60 , P=0.002) and a relative fluorescence intensity of 1.0±0.3 ( t=5.20, P<0.001). In contrast to the control group where only a small number of Gli1 positive cells were consistent with the distribution of H-type vessels, in the OTM group the number of Gli1 positive cells increased on the tension side were closely associated with the spatial distribution of H-type vessels. GO enrichment analysis of biological processes found that a large number of proteins in Gli1 positive cells were enriched in pathways such as angiogenesis and tissue remodeling. KEGG enrichment analysis found that related proteins were mainly enriched in pathways related to angiogenesis and Gli1, such as hypoxia-inducing factor 1 signaling pathway, vascular endothelial growth factor signaling pathway and hedgehog signaling pathway. Conclusions:The number of Gli1 positive cells increased on tension side and were closely related to H-type blood vessels in response to mechanical force during orthodontic tooth movement. This may be related to profile of inducing blood vessel formation and tissue remodeling.

Objective To compare the differences in thickness and fitting accuracy between direct-printed aligners(DPA)and conventional thermoformed aligners(TFA),and to provide experimental evidence for the clinical application of clear aligners(CAs).Methods Sixteen adult subjects with mild dental crowding and no significant caries or restorations were recruited.For each subject,CAs were fabricated using direct three-dimensional(3D)printing and conventional thermoforming methods.The CA thickness was measured at the labial/buccal and lingual surfaces of incisors,canines,and first molars using a high-precision electronic thickness gauge.Micro-CT scanning was employed to analyze the gap between the CAs and dental models,followed by statistical analyses.Results The overall mean thickness of the DPA group was(0.60±0.04)mm,significantly higher than that of the TFA group(0.48±0.06)mm(P＜0.000 1),with superior thickness uniformity.The average gap between CAs and dental models in the DPA group was(0.29±0.08)mm,significantly smaller than that in the TFA group(0.31±0.16)mm(P＜0.05),particularly at the incisal edges of incisors,buccal surfaces of canines,and occlusal surfaces of first molars.Conclusions Compared to conventional TFA,DPA demonstrates significant advantages in thickness uniformity and fitting accuracy,indicating that DPA has greater application potential in orthodontic clinical treatment.

This study investigated the types and distribution of rodents,and the infection status of eight pathogens in the high-altitude areas of western Sichuan,to provide a basis for control of rodent-borne diseases and pathogen surveillance in rodents in the area.From August to November of 2023,rodents were captured through the night method in high-altitude areas of western Sichuan.Nucleic acids were collected from the rodents'livers and lungs,and eight important pathogens were detected:Dabie bandavirus,Han-tavirus,Bartonella,Francisella tularensis,Anaplasma phagocytophilum,Rickettsia mooseri,Orientia tsutsugamushi,and Leptospira interrogans.The chi-square test was used to compare the composition ratios of rodent species and the difference in pathogen positivity rates among groups.A total of 114 rodents of nine species were captured.The dominant species in this area were Apodemus agrarius(22.81%),Apodemus chevrieri(18.42%),Niviventer confucianus(17.54%),Apodemus latronum(16.67%),and Apodemus peninsu-lae(13.16%).Other rodent species included Rattus nitidus(4.39%),Neodon irene(4.39%),Chodsigoa hypsibia(1.75%),and Nivi-venter excelsior(0.88%).Statistically significant differences in rodent species composition were observed among regions,altitudes,and habitats(χ2Region=112.358,P<0.05;χ2Altitude=96.843,P<0.05;χ2Habitat=48.842,P<0.05).The liver and lung pathogen results showed that the positivity rate of Bartonella was highest(29/114),whereas those of the other seven pathogens were 0%-4.39%.Five rodents were co-infected with two or more pathogens,and the composite positivity rate was 4.36%(5/114).Statistically significant differences in the positivity rates were observed for Leptospira interrogans among species(χ2=6.568,P=0.028)and Anaplasma phagocytophilum among habitats(χ2=7.596,P=0.027);however,no significant differences in the positivity rates of other pathogens were found among rodent species,regions,altitudes,habitats,and sexes(P>0.05).Thus,rodent species were abundant in the high-altitude areas of western Sichuan and carried a variety of pathogens.Multiple pathogens showed compound infections,among which the positivity rate of Bartonella was relatively high.The total infection rate of pathogens in living areas was relatively high,and the risk of pathogenesis to the population is greater.Therefore,rodent control and disease monitoring efforts should be strengthened.

Objective:To explore the relationship between the dark triad, fear of missing out and smartphone addiction, as well as the mediating role of fear of missing out between the dark triad and smartphone addiction.Methods:A total of 408 college students were assessed using dirty dozen, fear of missing out scale, and mobile phone addiction index. SPSS 24.0 software was used for common method bias tests, descriptive statistical analysis, and correlation analysis. Mplus 8.3 software was employed to construct a structural equation model, and the Bootstrap method was used for mediation effect analysis.Results:The dark triad (36.14±9.06) was positively correlated with fear of missing out (22.55±6.60) and smartphone addiction (46.77±13.62) ( r=0.48, 0.45, both P<0.01). Fear of missing out was also positively correlated with smartphone addiction ( r=0.54, P<0.01). Fear of missing out played a partial mediating role in the relationship between the dark triad and smartphone addiction, with a total effect value of 0.495 and a mediating effect value of 0.217. Conclusion:Fear of missing out partially mediates the relationship between the dark triad and smartphone addiction. The dark triad not only directly predicts smartphone addiction but also indirectly influences smartphone addiction through fear of missing out.

Objective:To explore the distribution characteristics of glioma-associated oncogene homolog 1 (Gli1) positive cells during orthodontic tooth movement process and conduct a proteomic analysis of these cells.Methods:Forty Gli1-LacZ transgenic mice were used to establish an in vivo orthodontic tooth movement (OTM) model for labeling Gli1 positive cells in Gli1-LacZ transgenic mice (OTM group) and an unforced control group, with tooth movement distance measured using micro-CT. The spatial relationship and distribution characteristics of Gli1 positive cells and H-type vessels of CD31 and endomucin (EMCN) in periodontal tissues were detected by immunofluorescence staining. Twenty Gli1-membrane-targeted tandem dimer Tomato (mT)/membrane-targeted green fluorescent protein (mG) double-genotype mice were bred and Gli1 positive cells were sorted for proteomic sequencing after tamoxifen induction. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used for enrichment analysis. Results:The micro-CT three-dimensional reconstruction results showed that the mesial movement of the maxillary first molar in mice after 7 days of force application was (69±15) μm, indicating the successful establishment of the Gli1-LacZ transgenic mouse OTM model. Immunofluorescence staining showed that the blood vessels in periodontal tissue were mostly H-type vessels of CD31 and EMCN. The blood vessels in the periodontal tissues are predominantly H-type vessels positive for both CD31 and EMCN. The percentage of Gli1 positive cells in the OTM group, expressed as (54.5±13.2)%, and the relative fluorescence intensity, expressed as 2.6±0.9, were both significantly greater than those in the control group, which had a Gli1 positive cell percentage of (36.3±9.1)% ( t=3.60 , P=0.002) and a relative fluorescence intensity of 1.0±0.3 ( t=5.20, P<0.001). In contrast to the control group where only a small number of Gli1 positive cells were consistent with the distribution of H-type vessels, in the OTM group the number of Gli1 positive cells increased on the tension side were closely associated with the spatial distribution of H-type vessels. GO enrichment analysis of biological processes found that a large number of proteins in Gli1 positive cells were enriched in pathways such as angiogenesis and tissue remodeling. KEGG enrichment analysis found that related proteins were mainly enriched in pathways related to angiogenesis and Gli1, such as hypoxia-inducing factor 1 signaling pathway, vascular endothelial growth factor signaling pathway and hedgehog signaling pathway. Conclusions:The number of Gli1 positive cells increased on tension side and were closely related to H-type blood vessels in response to mechanical force during orthodontic tooth movement. This may be related to profile of inducing blood vessel formation and tissue remodeling.