Objective: To examine the association between frailty and cognitive function in middle-aged and elderly populations using group-based trajectory model (GBTM), so as to provide insights into the prevention and intervention strategies for cognitive impairment in this population. Methods: From 2011 to 2018, data of demographic information and lifestyle behavior for individuals aged ≥45 years were collected from the China Health and Retirement Longitudinal Study. Frailty status was assessed using the frailty index, and cognitive function was evaluated using the Chinese version of the Mini-Mental State Examination. GBTM was applied to establish frailty trajectories based on the frailty index from 2011 to 2018 to analyze the trajectory of frailty changes. The association between frailty and cognitive function was analyzed using multiple linear regression model. Results: A total of 4 809 participants were included, with a mean age of (56.63±7.73) years. There were 2 621 males (54.50%) and 2 188 females (45.50%). The 2018 survey identified 574 individuals (11.94%) with cognitive function decline. GBTM identified four distinct frailty trajectories including the normal and stable group (69.27%), recovering frail group (9.32%), progressing pre-frail group (16.20%) and persistently frail group (5.22%). The mean cognitive funtion scores for these groups were (17.24±4.83) (16.38±5.53) (15.74±5.20) (15.02±5.11) points, respectively. The differences in cognitive funtion scores across groups were statistically significant (P<0.05). Multiple linear regression analysis showed, after adjusting for confounding factors such as gender, age, nighttime sleep duration, and smoking, compared with the normal and stable group, the cognitive function decline risk was higher in the frailty recovery group (β=-0.581), the pre-frail progression group (β=-0.583), and the persistently frail group (β=-0.662) compared with the non-frail stable group (all P<0.05). Conclusions There are four groups of changes in frailty among the middle-aged and elderly populations. Compared with the normal and stable group, the groups experiencing progression, persistence, and recovery of frailty exhibit a more pronounced risk of cognitive funtion decline.

Objective: To analyze the association between altitudes and nutritional status of children and adolescents, and to explore the moderating effects of dietary behaviors and physical activity, so as to provide a scientific basis for developing lifestyle interventions tailored to local conditions. Methods: From September to November 2023, physical examinations and questionnaire surveys were conducted among children and adolescents aged 7-17 in two autonomous regions, Inner Mongolia and Xizang, with a final sample of 156 511 participants by the stratified cluster random sampling method. Height and weight were measured to calculate body mass index (BMI). Sociodemographic characteristics, dietary behaviors, and physical activity were collected via questionnaires, while the altitude of each participant s school was obtained using Amap. Logistic regression was performed to examine the relationship between altitudes and nutritional status. Interaction terms and stratified analyses were applied to assess the moderating effects of dietary behaviors and physical activity. Restricted cubic spline (RCS) were used for visualization. Results: In 2023, the prevalence of wasting and overweight/obesity among children and adolescents in Xizang were 9.7% and 9.0%, respectively, compared to 2.9% and 22.0% in Inner Mongolia. Logistic regression analysis results showed that for every 1 km increase in altitude, the risk of wasting increased, while the risk of overweight/obesity decreased ( OR =1.43, 0.19, both P <0.05). The results of the stratified analysis showed that compared to those living at altitudes <1 km, children and adolescents with healthy diets showed no significant association between altitudes (1-<2 and 2-<3 km) and wasting ( OR =1.22, 0.75, both P >0.05), whereas significant associations were observed at 3-<4 and ≥4 km altitudes ( OR =2.25, 2.89, both P <0.05). In contrast, unhealthy dietary groups showed statistically significant associations across altitudes ( OR =1.18-4.04, all P <0.05), consistent with RCS results. No moderating effects were observed for physical activity on the altitude wasting association or for dietary behaviors and physical activity combined on the altitude overweight/obesity association ( P interaction =0.63, 0.10, 0.53). Conclusion Healthy dietary behaviors play a critical role in improving the nutritional status of children and adolescents and reducing regional disparities, providing a scientific foundation for public health policy formulation and implementation.

Identifying drug-drug interactions (DDIs) is essential to prevent adverse effects from polypharmacy. Although deep learning has advanced DDI identification, the gap between powerful models and their lack of clinical application and evaluation has hindered clinical benefits. Here, we developed a Multi-Dimensional Feature Fusion model named MDFF, which integrates one-dimensional simplified molecular input line entry system sequence features, two-dimensional molecular graph features, and three-dimensional geometric features to enhance drug representations for predicting DDIs. MDFF was trained and validated on two DDI datasets, evaluated across three distinct scenarios, and compared with advanced DDI prediction models using accuracy, precision, recall, area under the curve, and F1 score metrics. MDFF achieved state-of-the-art performance across all metrics. Ablation experiments showed that integrating multi-dimensional drug features yielded the best results. More importantly, we obtained adverse drug reaction reports uploaded by Xiangya Hospital of Central South University from 2021 to 2023 and used MDFF to identify potential adverse DDIs. Among 12 real-world adverse drug reaction reports, the predictions of 9 reports were supported by relevant evidence. Additionally, MDFF demonstrated the ability to explain adverse DDI mechanisms, providing insights into the mechanisms behind one specific report and highlighting its potential to assist practitioners in improving medical practice.

Objective To analyze the morphology of the pterygoid hamulus and its relationship with adjacent tissues on CBCT ima-ges,establish reference data of the anatomical structure of the pterygoid hamulus in the adult population,in order to provide a basis for clinical assisted diagnosis and treatment of pterygoid hamulus syndrome and obstructive sleep apnea hypopnea syndrome.Methods A total of 151 patients with CBCT images who met the inclusion criteria were collected from August 2020 to December 2023 in the Depart-ment of Stomatology at the Second Traditional Chinese Medicine Hospital of Jiangsu Province.The CBCT images were reconstructed u-sing the maximum intensity projection(MIP)and volume rendering(VR)modes of cone-beam CT.The morphology,length,width,vertical height,abduction angle,mucosal thickness,distance from the pterygoid hamulus to the midline of the palate,and distance from the pterygoid hamulus to the greater palatine foramen were observed and statistically analyzed in 302 bilateral cases.The differ-ences in the morphology of the pterygoid hamulus and its adjacent tissues were analyzed in different places,genders and age groups.Results The apex of the pterygoid hamulus faced inward on 6 sides and outward on 296 sides.The apex of the pterygoid hamulus was sharp on 46 sides and blunt on 256 sides.The pterygoid hamulus showed no statistically significant differences in various parameters be-tween the left and right sides,except for the width.In males,the length,width,height,distance from the pterygoid hamulus to the mid-palatal suture,and mucosal thickness on the surface of the hamulus were all greater than those in females,demonstrating statisti-cally significant differences.Females also exhibited a larger outward angle of the pterygoid hamulus than males,which was statistically significant.Moreover,with the increase of age,the length and height of the pterygoid hamulus initially increased and then decreased,exhibiting statistically significant differences.Conclusion CBCT has the advantages of low radiation dosage,convenient operation,clear imaging,stable measurement data,and clear images in the examination of pterygoid hamulus.It helps in the diagnosis and treat-ment of pterygoid hamulus-related diseases in a clinical setting.

Objective To investigate the therapeutic effect of Liangxue-jiedu decoction on acute-on-chronic liver failure(ACLF)model mice and the Toll-like receptor 4(TLR4)/c-Jun amino terminal kinase(JNK)/nuclear factor κB(NF-κB)signaling pathway.Methods An ACLF mouse model was established using combined treatment of carbon tetrachloride,lipopolysaccharide,and D-galactosamine.Biochemical analysis was performed to evaluate liver function indicators,including alanine aminotransferase,aspartate aminotransferase,and total bilirubin.Histopathological examination was conducted to assess liver tissue morphological changes.Quantitative PCR was used to detect the mRNA expression of tumor necrosis factor alpha(TNF-α),interleukin(IL)-6,IL-1 β,and TLR4 in liver tissues.A CCK8 assay was used to evaluate the optimal interventional concentration of Liangxue-jiedu decoction on Raw 264.7 cells.Enzyme-linked immunosorbent assay was used to detect the contents of TNF-α,IL-6,and IL-1βin the cell supernatant.Protein immunoblotting was performed to measure the expression of TLR4/JNK/NF-κB signaling pathway-related proteins,including TLR4,NF-κB,p-ERKl/2,ERK1/2,p-JNK,and JNK.Results Compared with the ACLF model group,the Liangxue-jiedu decoction-treated group showed reduced cell necrosis,fibrosis,and inflammatory cell infiltration in liver tissues;decreased serum levels of alanine aminotransferase,aspartate aminotransferase and total bilirubin;and lower expression of TNF-α,IL-6,IL-1β,and TLR4 mRNA.Liangxue-jiedu decoction reduced TLR4/JNK/NF-κB signaling pathway-related protein expression in liver tissues.The in vitro result also showed that Liangxue-jiedu decoction reduced TNF-α,IL-6,and IL-1 β secretion by macrophage cells and down-regulated the expression of TLR4/JNK/NF-κB signaling pathway proteins.Conclusions Liangxue-jiedu decoction effectively improved liver function in ACLF mice in a manner closely related to the downregulation of TLR4/JNK/NF-κB pathway proteins.

BACKGROUND: Previous studies have examined the bulk transcriptome of peripheral blood immune cells in acquired immunodeficiency syndrome patients experiencing immunological non-responsiveness. This study aimed to investigate the characteristics of specific immune cell subtypes in acquired immunodeficiency syndrome patients who exhibit immunological non-responsiveness. METHODS: A single-cell transcriptome sequencing of peripheral blood mononuclear cells obtained from both immunological responders (IRs) (CD4 + T-cell count >500) and immunological non-responders (INRs) (CD4 + T-cell count <300) was conducted. The transcriptomic profiles were used to identify distinct cell subpopulations, marker genes, and differentially expressed genes aiming to uncover potential genetic factors associated with immunological non-responsiveness. RESULTS: Among the cellular subpopulations analyzed, the ratios of monocytes, CD16 + monocytes, and exhausted B cells demonstrated the most substantial differences between INRs and IRs, with fold changes of 39.79, 11.08, and 2.71, respectively. In contrast, the CD4 + T cell ratio was significantly decreased (0.39-fold change) in INRs compared with that in IRs. Similarly, the ratios of natural killer cells and terminal effector CD8 + T cells were also lower (0.37-fold and 0.27-fold, respectively) in the INRs group. In addition to several well-characterized immune cell-specific markers, we identified a set of 181 marker genes that were enriched in biological pathways associated with human immunodeficiency virus (HIV) replication. Notably, ISG15 , IFITM3 , PLSCR1 , HLA-DQB1 , CCL3L1 , and DDX5 , which have been demonstrated to influence HIV replication through their interaction with viral proteins, emerged as significant monocyte marker genes. Furthermore, the differentially expressed genes in natural killer cells were also enriched in biological pathways associated with HIV replication. CONCLUSIONS We generated an atlas of immune cell transcriptomes in HIV-infected IRs and INRs. Host genes associated with HIV replication were identified as markers of, and were found to be differentially expressed in, different types of immune cells.
Humans ; Acquired Immunodeficiency Syndrome ; Transcriptome/genetics* ; HIV ; HIV Infections/genetics* ; Leukocytes, Mononuclear/metabolism* ; CD4-Positive T-Lymphocytes/metabolism* ; Virus Replication ; Membrane Proteins/metabolism* ; RNA-Binding Proteins/metabolism*

OBJECTIVE: To determine the types and frequency of deafness-related variants among 7875 newborns from Dongying area of Shandong Province. METHODS: One hundred loci of 18 common deafness genes were subjected to semiconductor sequencing. Variant site, frequency and distribution of the variants were analyzed. RESULTS: In total 552 deafness gene variants were detected among the 7875 newborns, which yielded a detection rate of 7.01%. Among these, common variant sites for GJB2, SLC26A4 and GJB3 genes were c.235delC, IVS7-2A>G and c.538C>T, respectively. The variant frequencies of matrilinear inheritance deafness genes MT-CO1, MT-RNR1, MT-TL1 and MT-TS1 were 0.38%, 0.25%, 0.1% and 0.01%, respectively. Four newborns were diagnosed with deafness, among which one had unilateral hearing loss. Analysis of the proportions of neonatal deafness-related variants in five counties of Dongying showed that the highest variant rate for the SLC26A4 gene compared with GJB2 was in Lijin county (51.76% vs. 40%), while the lowest was in Hekou county (30.77% vs. 56.41%). CONCLUSION The carrier rate of deafness-related variants in Dongying area is higher than other regions of China, which may be attributed to the increased types and variant sites covered by the semiconductor sequencing method compared with the chip method and time-of-flight mass spectrometry. Due to geographical and population aggregation factors, the proportion of deafness variants in the five counties of Dongying differed significantly. Above results may provide a guide for the prevention of congenital deafness in Dongying area.

Objective To investigate the co-transfection of p53 and angiostatin gene in the inhibition of SG7901. Methods Transfected the pVITRO2-hp53-hAS into SG7901 with lipofectamine.After transfection, RT-PCR were used to know whether the aimed gene had been transfected and expressed or not. Cell clones trial, MTT growth curve, cell cycle measuring were used to analyze the differences. Results The cells were suppressed by the two genes and inhibition of the combined genes is more powerful than single one. Conclusion The effection of combined genes pVITRO2-hp53-hAS on SG7901 is stronger than either single one. Combined-gene-therapy is a useful anti-carcinoma method.