ObjectiveThis study aims to investigate the effect of Liuwei Dihuangwan on the autophagy function in the hippocampus of senescence-accelerated mouse prone 8 （SAMP8） by regulating the expression of glycoprotein non-metastatic melanoma protein B （GPNMB）. Furthermore， it is designed to explore the mechanism of the method of tonifying the kidneys and replenishing essence in the treatment of Alzheimer's disease （AD）. MethodsIn experiment 1， 24 5-month-old SAMP8 mice were randomly and equally divided into the model group， and the low-， middle- and high-dose（0.59，1.18，2.36 g·kg^-1） Liuwei Dihuangwan groups. At the same time， six 5-month-old senescence accelerated mouse resistant 1 （SAMR1） mice were used as the control group. The learning and memory ability was evaluated through novel object recognition experiment. Serum cortisol （Cort）， adrenocorticotropic hormone （ACTH） and urine 17-hydroxycorticosteroid （17-OHCS） levels were detected by enzyme-linked immunosorbent assay （ELISA）. The ultrastructure of hippocampal neurons was observed by transmission electron microscope （TEM）， and the expression levels of hippocampal GPNMB， a disintegrin and metalloproteinase 10 （ADAM10） and autophagy-related proteins were detected by Western blot. In experiment 2， 18 SAMP8 mice were randomly and equally divided into the model group， vector control group （Vector）， and GPNMB overexpression group （GPNMB^OE）. Lentiviral vectors were stereotactically injected into the brain （2 μL per side in the GPNMB^OE group）. Western blot was used to detect the expression of the above target proteins in the hippocampus； In Experiment 3， 24 SAMP8 mice were randomly and equally divided into the model group， Liuwei Dihuangwan group， Liuwei Dihuangwan+negative control （NC） group， and Liuwei Dihuangwan+GPNMB silencing group （shGPNMB）. Before drug treatment， the Liuwei Dihuangwan+NC group and the Liuwei Dihuangwan+shGPNMB group were injected with negative control and GPNMB silencing lentivirus， respectively. Western blot was used to detect the expression of the above target proteins in the hippocampus. ResultsThe novel object discrimination index of mice in the model group was significantly lower than that of mice in the control group （P<0.01）. The novel object discrimination index of mice in the medium- and high-dose Liuwei Dihuangwan groups was significantly higher than that of mice in the model group （P<0.01）. Aggregated autolysosomes were observed in the normal hippocampus tissue by TEM. In the model group， mitochondria were dominant， and no typical characteristic autophagosomes were observed. In the low- and medium-dose Liuwei Dihuangwan groups， a small number of autolysosomes and autophagosomes with double-membrane structures were observed. In the high-dose Liuwei Dihuangwan group， the number of autophagosomes and autolysosomes was greater than that in the low- and medium-dose groups. The results of ELISA and Western blot showed that compared with the control group， the levels of serum Cort， ACTH， and urine 17-OHCS in the model group were substantially increased， while the expression of hippocampal ADAM10， Beclin1， and microtubule associated-protein light chain 3-Ⅱ/Ⅰ （LC3 Ⅱ/Ⅰ） was significantly decreased. The expression of GPNMB and ubiquitin binding protein p62 was significantly increased （P<0.05， P<0.01）. Compared with the model group， the serum Cort and ACTH levels in the low-， medium-， and high-dose Liuwei Dihuangwan groups were significantly reduced， while only the urine 17-OHCS level in the high-dose group was significantly reduced. The hippocampal GPNMB， ADAM10， Beclin1， and LC3 Ⅱ/Ⅰ expression levels in the medium-， and high-dose groups of Liuwei Dihuangwan were significantly increased compared to the model group， whereas the expression of p62 was significantly reduced （P<0.01）. The above indicators showed a progressive trend among the three groups. Compared with the model group， the GPNMB^OE group showed a significant increase in GPNMB， ADAM10， Beclin1， LC3 Ⅱ/Ⅰ expression， and a significant decrease in p62 expression （P<0.01）. Compared with the model group， the expression of GPNMB， ADAM10， Beclin1， and LC3 Ⅱ/Ⅰ in the hippocampus of the Liuwei Dihuangwan group significantly increased， while the expression of p62 significantly decreased （P<0.01）. Compared with the Liuwei Dihuangwan group， the Liuwei Dihuangwan+shGPNMB group showed a significant decrease in GPNMB， ADAM10， Beclin1， LC3 Ⅱ/Ⅰ， and a significant increase in p62 expression （P<0.01）. ConclusionLiuwei Dihuangwan can enhance hippocampal autophagy function and improve AD by upregulating GPNMB expression.

Background: Visual impairment is increasingly prevalent, underscoring the need for effective prevention strategies. This study investigated the association between cardiovascular health and visual impairment using three progressively developed metrics: Life’s Simple 7 (LS7), a cardiovascular health score developed by the American Heart Association based on 7 components, including physical activity, smoking status, body mass index (BMI), diet, blood glucose, blood pressure, and total cholesterol; Life’s Essential 8(LE8), which adds sleep health as an additional component; and Life’s Crucial 9 (LC9), which further incorporates mental health. We aimed to evaluate whether these expanded metrics provide additional explanatory value and to inform future public health strategies. Objective: To investigate the associations among LS7, LE8, and LC9 cardiovascular health scores and visual impairment in National Health and Nutrition Examination Survey 2013 to 2018, assess the added value of sleep and mental health components, and identify key contributing subcomponents using regression and machine learning methods. Methods: We analyzed data from 9891 participants in the 2013 to 2018 National Health and Nutrition Examination Survey. Multivariable logistic regression, restricted cubic spline modeling, and subgroup analyses were conducted to evaluate the association between cardiovascular health and visual impairment. Machine learning methods, including Random Forest and SHapley Additive exPlanations, a model interpretation approach used to assess feature importance, were applied. The Boruta algorithm, a feature selection method, was used to identify key subcomponents of cardiovascular health. Results: Participants with visual impairment were older, had lower poverty-to-income ratios, and exhibited lower cardiovascular health scores (LS7, LE8, and LC9). Higher cardiovascular health scores were negatively associated with visual impairment. Each one standard deviation increase in LS7, LE8, and LC9 was associated with approximately 8%, 2%, and 3% lower odds of visual impairment, respectively. LS7 showed the strongest negative association, whereas LE8 and LC9 emerged as the most important predictors in the machine learning models. Key subcomponents such as blood glucose, blood pressure, and BMI, as well as mental health status, were strongly associated with visual impairment. Conclusion: Higher cardiovascular health scores were negatively associated with visual impairment. LS7 demonstrated the strongest statistical association, whereas LE8 and LC9 were the most influential features in the machine learning models. Blood glucose, blood pressure, BMI, and mental health status were important correlates of visual impairment. From the perspective of the “prevention and treatment of diseases” in traditional Chinese medicine and the holistic concept, the aforementioned research findings confirm that severe visual impairment is indeed an external manifestation of overall health imbalance (such as organ dysfunction and Qi deficiency and blood stasis). The prevention strategy lies in comprehensively adjusting lifestyle, emotional factors, and metabolic indicators (corresponding to the key factors in the study) to restore the body’s internal balance and achieve prevention before disease arises.

Objective To study the effect of Liuwei Dihuangwan on autophagy level and its mechanism in SAMP8 mice and Aβ-stimulated BV2 cell model,and to explore the molecular mechanism of tonifying the kidney and filling up the essence to prevent and control Alzheimer's disease(AD)through interfering with autophagy.Methods Ten 7-month-old male anti-aging mice(SAMR1)were taken as the normal group,and 40 7-month-old male rapid aging mice(SAMP8)were randomly control and model groups,equal volumes of saline were administered by gavage twice a day for 4 weeks,and the levels of Aβ expression in the hippocampus of the mice in each group were detected by immunofluorescence;The expression levels of FcγRⅡB,c-Src and SHP-1 in the hippocampus of each group were detected by Western blot;BV2 cells were cultured and Fcγ receptor Ⅱ-b(FcγRⅡB)overexpression vectors were constructed;the AD state cell model was established by treating the BV2 cells with 5 μmol·L-1 Aβ1-42,and the Liuwei Dihuangwan drug-containing serum was prepared.The cells were divided into NC group,Aβ1-42 group,blank serum group,drug-containing serum group,Vector group,FcγRⅡB OE group,and drug-containing serum+FcγRⅡB OE group;immunofluorescence was used to detect the expression level of Aβ protein in the cells of each group;Western blot was used to detect the expression level of p62,LC3 Ⅱ/Ⅰ,FcγRⅡB,SHP-1,and c-Src in cells of each group.Results Compared with the normal group,the hippocampal Aβ,FcγRⅡB,SHP-1,and c-Src expression levels in the model group of mice were significantly higher(P<0.01),and compared with the model group,the expression levels of Aβ,FcγRⅡB,SHP-1,and c-Src in the low-,medium-,and high-dose groups of Liuwei Dihuangwan were significantly lower(P<0.01),it also showed a significant dose dependent relationship.Compared with NC group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in Aβ1-42 group were significantly increased(P<0.01),and LC3Ⅱ/Ⅰ was significantly decreased(P<0.01);Compared with Aβ1-42 group and blank serum group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in drug-containing serum group were significantly decreased(P<0.01),and LC3Ⅱ/Ⅰ was significantly increased(P<0.01);Compared with NC group and Vector group,the expression of Aβ in FcγRⅡB OE group was increased,the protein expressions of p62,FcγRⅡB,SHP-1 and c-Src were significantly increased(P<0.01),and LC3Ⅱ/Ⅰ was significantly decreased(P<0.01);Compared with the drug-containing serum group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in the drug-containing serum+FcγRⅡB OE group were significantly increased(P<0.01),and the protein expression levels of LC3Ⅱ/Ⅰ were significantly decreased(P<0.01).Conclusion Liuwei Dihuangwan improved AD by inhibiting microglia FcγRⅡB/c-Src pathway and increasing autophagy level.

Objective:To study the relationship between the levels of multiple elements in urine and the risk of arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region (Inner Mongolia).Methods:From April 2023 to January 2024, a case-control study method was used to select 128 individuals with a residence time of ≥10 years in drinking water arsenic exposed areas in Inner Mongolia as study subjects. Eighty-one individuals diagnosed with arsenic poisoning were selected as the case group, and 47 healthy individuals were selected as the control group for urine sample collection and questionnaire survey. Inductively coupled plasma mass spectrometry was employed to determine the levels of 10 elements (chromium, manganese, cobalt, nickel, copper, zinc, arsenic, molybdenum, cadmium and lead) in urine. The levels of each element in urine were divided into four groups ( Q1, Q2, Q3, and Q4 groups) based on quartiles. The associations between the levels of various elements in urine and the risk of arsenic poisoning were studied using binary logistic regression model and restricted cubic spline (RCS). Results:The age of the control group and the case group [ M ( Q1, Q3)] were 61 (53, 69) and 61 (56, 67) years old, respectively. There were 19 and 43 males, and 28 and 38 females, respectively. There was no statistically significant differences in age and and gender composition between the two groups ( Z = - 0.39, P = 0.700; χ 2 = 1.91, P = 0.167). The levels of urinary copper and cadmium of the case group were higher than those of the control group, and the differences were statistically significant ( Z = - 2.66, - 2.16, P < 0.05). The results of univariate logistic regression analysis showed that urinary copper was an influencing factor for arsenic poisoning ( P = 0.017). The results of multivariate logistic regression analysis revealed that after adjusting for covariates, urinary copper and arsenic were independent influencing factors of arsenic poisoning ( P < 0.05). Taking Q1 group as a reference, urinary copper in Q3 group [ OR (95% CI) = 8.23 (1.81, 37.39), P = 0.006] increased the risk of arsenic poisoning, while urinary arsenic in Q2, Q3, and Q4 groups [ OR (95% CI) = 0.24 (0.06, 0.92), 0.12 (0.03, 0.53), 0.15 (0.04, 0.63), P < 0.05] decreased the risk of arsenic poisoning. After adjusting for covariates, RCS did not show a dose-response relationship between urinary copper, urinary arsenic, and arsenic poisoning ( P > 0.05). Conclusion:Urinary arsenic and copper are associated with the risk of arsenic poisoning in the drinking water arsenic exposed areas of Inner Mongolia, copper exposure may contribute significantly to arsenic poisoning.

Objective:To construct an indicator system for entrustable professional activities (EPAs) in the general practice enhancement stage of pediatric specialist physician training.Methods:A draft indicator system for EPAs in the general practice enhancement stage of pediatric physician training was developed through core EPAs working group discussion, literature review, nominal group discussion, and expert consultation. Subsequently, the indicator system was preliminarily implemented and revised.Results:The core EPAs working group consisted of nine specialist physician trainers. In the initial brainstorming stage, a "potential list" of 30 activities was established. After literature review and collation, the draft indicator system included eight EPAs. Through nominal group discussion, the connotation of the draft was enriched, and the importance of the EPAs was ranked and modified. Finally, through expert consultation, the EPAs for the general practice enhancement stage of pediatric specialist physician training were determined. These included basic operations for the treatment of critically ill children, identification and management of critical illnesses, referral of critically ill children, perioperative management, in-hospital consultation, medical and teaching management and system improvement, doctor-patient communication and dispute handling, and response to public health events. During the preliminary implementation stage, a total of nine specialist physicians who participated in the training were evaluated. Based on the problems found in the pre-evaluation, the indicators of EPAs were revised, and a corresponding curriculum training system was developed.Conclusions:Through multiple rounds of nominal group discussion and expert consultation, the indicator system for EPAs in the general practice enhancement stage of pediatric specialist physician training was formulated. The system was preliminarily implemented and revised, and a curriculum system was constructed.

Objective:To investigate the influencing factors of adult dental fluorosis in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region.Methods:A case-control study was conducted in January 2024 to select adult fluorosis patients (case group) and healthy individuals (control group) from the drinking water-borne endemic fluorosis areas in Helinger County, Hohhot City, Inner Mongolia Autonomous Region as the survey subjects. Urine samples were collected to determine urinary fluoride concentration. A questionnaire survey was conducted. SPSS 25.0 software was used for χ 2 test and multivariate logistic regression analysis. Restricted cubic spline (RCS) was used to analyze the association between urinary fluoride concentration and the risk of dental fluorosis in adults. Results:A total of 161 individuals were included in the survey, including 100 in the case group and 61 in the control group. The results of univariate analysis showed that there were statistically significant differences in the distribution of gender, smoking, and urinary fluoride concentration between the case group and the control group (χ 2 = 7.54, 5.02, 9.69, P < 0.05). The results of multivariate logistic regression analysis indicated that gender ( OR = 0.36, 95% CI: 0.18 - 0.73, P = 0.005) and urinary fluoride concentration ( OR = 3.08, 95% CI: 1.46 - 6.67, P = 0.003) were the influencing factors of adult fluorosis. RCS analysis showed a significant linear dose-response relationship between the risk of dental fluorosis and urinary fluoride concentration ( Poverall trend = 0.001, Pnonlinear = 0.071). When the urinary fluoride concentration was greater than 1.57 mg/L, the risk of dental fluorosis increased with the increase of urinary fluoride concentration. Conclusion:Gender and urinary fluoride concentration are the risk factors of dental fluorosis in adults in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region.

Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

BACKGROUND:Based on the principle of vertical tooth movement,a personalized orthodontic appliance is created through digital design combined with 3D printing,so that the personalized orthodontic appliance forms a support system with the individual incisors.With the help of the absolute support of the micro-implant,the single tooth is precisely controlled in a three-dimensional direction.OBJECTIVE:To design personalized orthodontic appliances with 11,12,21,and 22 intrusion and extrusion based on biomechanical principles,and analyze the safety of the personalized orthodontic appliances in terms of their movement effect on the teeth by means of the three-dimensional finite element method.METHODS:Three-dimensional finite element models of alveolar bone-periodontium-maxillary incisors-personalized cantilever micro-implant-connecting plates-personalized brackets in the maxillary anterior region(teeth numbers 11,12,21,and 22)were established using Mimics,Geomagic Wrap,SolidWorks,and Ansys Workbench software,respectively.Personalized orthodontic appliances with low pressure movement and extended movement were set up at each tooth position.The stress level of each component of the personalized orthodontic appliances was analyzed,and the tooth displacement and periodontal stress distribution were calculated under loading of 300 g tensile or thrust force.RESULTS AND CONCLUSION:(1)The maximum equivalent force on the personalized intrusion mobile orthodontic appliance was 162.90 MPa,and the maximum equivalent force on the personalized extrusion mobile orthodontic appliance was 239.57 MPa.The maximum equivalent stress on both devices was located in the vertical portion of the personalized bracket loading attachment.The equivalent stresses on each part of the personalized orthodontic appliance were all within the yield strength,and they had good safety.(2)The initial displacement of the teeth under the action of the personalized orthodontic appliances showed a tendency towards overall intrusion or extrusion,with the displacement in the vertical direction far exceeding that in the horizontal and sagittal directions.The equivalent stress peak appeared at the root tip or neck of the periodontal membrane,and the equivalent stress concentration area appeared in the periodontal membrane of the root apical region.(3)The results show that the personalized orthodontic appliance allows 11,12,21,and 22 to approximate either intrusion movement or extrusion movement,initially confirming the effectiveness of the personalized vertical movement orthodontic appliance.

BACKGROUND:Currently,the mandibular joint prosthesis manufactured at home and abroad needs to rely on screws to fix the condylar part of the prosthesis during the replacement process,and the retention hole is reserved to facilitate the operation during the operation.However,due to the lack of personalized jaw design,the reattachment plate may not fit the jaw,resulting in screw loosening and dislocation.Therefore,personalized condylar prosthesis replacement is of great value in the repair of the temporomandibular joint.OBJECTIVE:To design a personalized condylar prosthesis with an internal GYROID for mandibular condylar repair and reconstruction.METHODS:The GYROID structure was selected in the Rhinoceros 7 software with the single cell size of 6 mm and the wall thickness of 0.2,0.3,0.4,0.5,0.6,0.7,0.8 mm.The mechanical properties of the GYROID structure were analyzed by finite element method.3D printing of GYROID structural test specimens with different wall thickness(0.2,0.3,0.4,0.5,0.6,0.7,and 0.8 mm)was performed to test the mechanical properties of the specimens through room temperature compression experiments.A wall thickness value conforming to the range of mandibular mechanical properties was selected through finite element analysis and room temperature compression test results.An adult male mandibular CT data were used for inverse modeling to design a condylar prosthesis with an internal GYROID.Finite element analysis was used to simulate the movement of the apical staggered position and the opposite-blade jaw position after condylar prosthesis replacement.RESULTS AND CONCLUSION:(1)The results of finite element analysis and room temperature compression experiment showed that the elastic modulus of the GYROID structure increased with the increase of wall thickness.The elastic modulus of the GYROID structure with wall thickness of 0.5-0.7 mm was within the range of the elastic modulus of the mandible(1.5-4.0 GPa).Therefore,the 6 mm monocellular GYROID structural model with a wall thickness of 0.6 mm was selected for the design of the condylar prosthesis.(2)The results of finite element analysis showed that the stress distribution of mandibular model was symmetrical.The stress distribution of the two types of occlusion was roughly the same,and the stress peak was not significantly different.The stress concentrated in the neck of the condylar prosthesis,and the stress on the replacement side was slightly larger than that on the healthy side.The maximum equivalent stress of the whole internal fixation model was 269.34 MPa,and the maximum equivalent stress of the screw was 20.14 MPa.The equivalent stress and equivalent strain values of the prosthesis were greater than that of the opposite edge jaw position when the tooth tip was interlaced.The equivalent stress and equivalent strain values of the screw were smaller than that of the opposite edge jaw position when the tooth tip was interlaced.(3)The results showed that the design and retention of the personalized GYROID condylar prosthesis were good,which was consistent with the mechanical conduction of the mandible.

BACKGROUND:Porous structures based on triple periodic minimal surfaces are one of the most promising orthopedic biostructures,among which the Gyroid structure is characterized by high specific surface area,high permeability,and zero mean curvature.OBJECTIVE:To screen the wall thickness interval of TC4 bionic bone scaffolds with 4 mm single-cell Gyroid structure matching the elastic modulus range of cancellous bone of the mandible through finite element analysis combined with mechanical compression test testing.METHODS:The finite element model of the 4 mm single-cell Gyroid structure with different wall thickths(0.1,0.2,0.3,0.4,0.5,0.6,0.7,and 0.8 mm)was established.The equivalent elastic modulus of the Gyroid structure was analyzed,and the wall thickness interval of the Gyroid structure matching the elastic modulus range of the maxillary resinous bone was selected with different wall thicknesses of 0.2,0.3,0.4,0.5,0.6,and 0.7 mm,respectively.According to finite element analysis screening results,the material selected was Ti6Al4V.Selective laser melting was used to prepare 3D printed Gyroid structure specimens.The surface treatment was carried out by large-grained sand blasting and acid etching.The elastic modulus and compressive strength of the specimen were tested by mechanical compression experiment.RESULTS AND CONCLUSION:(1)The finite element analysis results showed that the equivalent elastic modulus of the Gyroid structure increased with the increase of wall thickness,and the equivalent elastic modulus of the Gyroid structure with wall thickness of 0.2-0.7 mm was within the range of the elastic modulus of the spongy bone of the mandible(1.5-4.0 GPa),which was used for 3D printing of the Gyroid structure specimen.(2)The mechanical compression test results showed that the elastic modulus and compressive strength of the Gyroid structural specimen increased with the increase of wall thickness,and the elastic modulus of the Gyroid structural specimen with wall thickness of 0.3-0.5 mm was within the range of the elastic modulus of the cancellous bone of the mandible.The compressive strength of the Gyroid specimen with 0.3-0.7 mm wall thickness was consistent with the mechanical properties of the mandible.(3)The results show that the Gyroid structure of 0.3-0.5 mm wall thickness is compatible with the range of elastic modulus of the mandible.