ObjectiveTo investigate the functional role and underlying molecular mechanisms of fumarylacetoacetate hydrolase （FAH） in the progression of glioblastoma （GBM）. MethodsDifferential expression analysis was performed on the TCGA-GBM， GSE4290， and GSE116520 datasets. Weighted gene co-expression network analysis （WGCNA） was used to identify key modules， and Cox regression and risk modeling were used to screen prognostic genes. Immune infiltration analysis of prognostic genes was carried out by using single-cell RNA sequencing panels. The clinical expression signature of FAH in GBM was analyzed in the TCGA and HPA databases. The functional role of FAH was validated by in vitro and in vivo experiments， and pathway analysis was performed to explore the underlying mechanisms. ResultsA total of 152 overlapping genes were identified across the three GBM datasets （P<0.05）. WGCNA revealed that the turquoise module was most strongly associated with tumor purity， stromal score， immune score， and ESTIMATE score （P<0.001）. Compared with normal tissues， three prognostic genes （CTSD， FAH， and THBD） were upregulated in GBM and correlated with immune infiltration （P<0.05）. FAH mRNA and protein levels were elevated in GBM tissues relative to normal tissues， and its expression was significantly associated with age stratification and TP53 mutation （P<0.05）. CCK-8 assay results showed that， compared with the shNC group， the proliferative activity of GBM cells in the shFAH group was reduced （P<0.001）. Transwell migration and invasion assays demonstrated that， relative to the shNC group， the numbers of migrated and invaded cells in the shFAH group decreased （P<0.05）. Western blot analysis revealed that the protein expression levels of PI3K， p-AKT， and p-mTOR in the shFAH group decreased compared with those in the shNC group （P<0.05）. In vivo subcutaneous xenograft experiments further confirmed that tumor volume and weight significantly decreased in the shFAH group compared with the shNC group （P<0.001）. ConclusionFAH promotes GBM progression by activating the PI3K/AKT/mTOR signaling pathway and may serve as a potential therapeutic target for GBM.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

Objective To systematically evaluate the impact of pulmonary hypertension (PH) on the prognosis of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Methods A computerized search was conducted in CNKI, Wanfang Data, VIP, CBM, PubMed, The Cochrane Library, EMbase, and Web of Science databases from inception to June 2023 for cohort studies on the prognostic impact of PH in severe AS patients undergoing TAVR. Two researchers independently screened the literature, extracted data, and assessed the quality of included studies. Stata 17.0 software was used for meta-analysis. Results A total of 16 cohort studies were included, all with Newcastle-Ottawa Scale scores≥7. Meta-analysis results showed that, compared with AS patients without PH, those with PH had significantly higher 1-year all-cause mortality after TAVR [OR=2.10, 95%CI (1.60, 2.75), P<0.01], 30-day all-cause mortality [OR=2.09, 95%CI (1.54, 2.83), P<0.01], and cardiovascular mortality [OR=1.49, 95%CI (1.18, 1.90), P<0.01]. The differences between the two groups in major bleeding events, stroke, myocardial infarction, pacemaker implantation, and postoperative renal failure were not statistically significant. For outcome indicators with significant heterogeneity, subgroup analyses were performed based on PH measurement methods, diagnostic criteria, and different types of PH. The results showed that most subgroup combined results were consistent with the overall findings and that heterogeneity was significantly reduced. Conclusion PH significantly increases the 30-day all-cause mortality, 1-year all-cause mortality, and cardiovascular mortality in patients with severe AS undergoing TAVR.

Objective: To examine the association between incidence of hand-foot-mouth disease (HFMD) and meteorological factors, so as to provide the basis for the prevention and control of HFMD. Methods: The number of HFMD cases in Jiading District, Shanghai Municipality from 2016 to 2023 were collected through the Chinese Disease Prevention and Control Information System, and meteorological data were obtained from the Shanghai Meteorological Bureau. The associations of daily average temperature, daily average relative humidity, and daily average atmospheric pressure with the daily number of HFMD cases were analyzed using a distributed lag non-linear model (DLNM). Results: A total of 21 555 HFMD cases were reported in Jiading District from 2016 to 2023, with an average annual incidence of 132.57/100 000. There were 12 762 male cases (59.21%) and 8 793 female cases (40.79%). The main peak of incidence occurred from June to August, and the secondary peak was from October to December. DLNM analysis showed that the incidence risk of HFMD first increased and then decreased with the increase of daily average temperature, and first decreased and then increased with the prolongation of the lag time. The cumulative lag risk was higher when the daily average temperature ranged from 18.4 to 35.1 ℃, and the maximum cumulative lag effect was observed at 27.8 ℃ (RR=5.522, 95%CI: 4.751-6.370). The incidence risk of HFMD first increased and then decreased with the increase of daily average relative humidity, and first decreased, then increased and then decreased again with the prolongation of the lag time. The cumulative lag risk was higher when the daily average relative humidity ranged from 71.7% and 90.8%, and the maximum cumulative lag effect was observed at 81.8% (RR=1.603, 95%CI: 1.321-1.995). The incidence risk of HFMD decreased with the increase of daily average atmospheric pressure, and decreased with the prolongation of the lag time when the daily average atmospheric pressure was greater than 1 015.80 hPa. When the daily average atmospheric pressure was less than 1 015.80 hPa, the incidence risk of HFMD increased with the prolongation of the lag time. The maximum cumulative lag effect was observed at 986.80 hPa (RR=8.513, 95%CI: 1.401-36.625). Conclusion The incidence risk of HFMD in Jiading District initially increases and then decreases with increasing temperature and relative humidity, while it decreases with increasing atmospheric pressure, and these effects exhibit a lagged response.

This study identified 8 members including NjBIN2 of the GSK3 family in Nardostachys jatamansi by bioinformatics analysis. Moreover, the phylogenetic tree revealed that the GKS3 family members of N. jatamansi had a close relationship with those of Arabidopsis. RT-qPCR results showed that NjBIN2 presented a tissue-specific expression pattern with the highest expression in roots, suggesting that NjBIN2 played a role in root growth and development. In addition, the application of epibrassinolide or the brassinosteroid(BR) synthesis inhibitor(brassinazole) altered the expression pattern of NjBIN2 and influenced the photomorphogenesis(cotyledon opening) and root development of N. jatamansi, which provided direct evidence about the functions of NjBIN2. In conclusion, this study highlights the roles of BIN2 in regulating the growth and development of N. jatamansi by analyzing the expression pattern and biological function of NjBIN2. It not only enriches the understanding about the regulatory mechanism of the growth and development of N. jatamansi but also provides a theoretical basis and potential gene targets for molecular breeding of N. jatamansi with improved quality in the future.
Brassinosteroids/metabolism* ; Steroids, Heterocyclic/metabolism* ; Gene Expression Regulation, Plant/drug effects* ; Plant Proteins/metabolism* ; Phylogeny ; Nardostachys/metabolism* ; Plant Growth Regulators/pharmacology* ; Plant Roots/drug effects*

The holistic view is the key in the study of traditional Chinese medicine(TCM). The component structure theory is based on the holistic view to investigate the correlation between material basis and efficiency, which enriches the holistic "component-effect" research of TCM. Gintonin is a newly isolated non-saponin component of ginseng. Compared to ginsenosides, gintonin has many different pharmacological activities, and it provides new knowledge for the holistic research of ginseng. Thus, taking the discovery of gintonin from ginseng as an example, this paper explored the linkage between ginsenosides and gintonin from the perspective of "component-effect" correlations and systematically sorted out the similarities and differences between them in terms of structural characteristics, modes of action, and pharmacological activities. Starting from the collaborative interaction of TCM compounds, the study discussed the application and value of the holistic view in TCM "component-effect" research in the light of the component structure theory to provide new thoughts for the development of modern TCM research.
Panax/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional ; Humans ; Ginsenosides/pharmacology* ; Animals

Objective: To understand the unhealthy listening habits and related factors hearing on impairment among primary and middle school students in Jilin Province, so as to provide a scientific basis for the prevention of hearing impairment in children and adolescents. Methods: From September to November 2021, a stratified cluster random sampling method was employed to select 12 847 primary and middle school students in nine cities of Jilin Province who use headphones for more than 0.5 hours daily for a questionnaire survey. Data on unhealthy listening habits, lifestyle habits and hearing impairment were collected. The data were analyzed using the χ 2 test and Logistic regression. Results: Totally 1 702 students(13.25%) experienced hearing impairment within the last month. There were statistical differences between the sexes with the average daily headphone use, the times of using headphones ≥1 h every day for one week use in all environment or noisy environment ( χ 2=47.86, 57.60, 66.31, P <0.01). Logistic regression analysis results showed that factors related to the occurrence of hearing impairment among primary and secondary school students included:average daily headphone use of 1-2 h and more than 2 h ( OR=1.74, 95%CI =1.60-1.90; OR=1.73, 95%CI =1.59-1.90), times of using headphones ≥1 h every day for one week were 1-2 times and >2 times ( OR=1.71, 95%CI =1.59- 1.84 ; OR=1.83, 95%CI =1.71-1.97), the times of using headphones≥1 h every day for one week being 1-2 times and >2 times in noisy environment per week ( OR=1.48, 95%CI =1.40-1.56; OR=1.72, 95%CI =1.61-1.86), economic underdevelopment ( OR=1.85, 95%CI =1.76-1.96), boarding （OR=1.78, 95%CI =1.69-1.89), single parent family ( OR=1.72, 95%CI =1.60- 1.87 ), daily activity duration less than 1 h ( OR=1.71, 95%CI =1.63-1.81), sedentary behavior duration more than 6 h per day ( OR=1.88, 95%CI =1.79-1.98) ( P <0.05). Conclusions The behavior of ear protection among primary and middle school students in Jilin Province needs to be enhanced, focusing on students in economically underdeveloped areas, boarding schools and single parent families. It is necessary to guide primary and middle school students to improve their bad ear habits, increase outdoor activities and reduce the time of sitting.

ObjectiveTo investigate the efficacy of ovarian tissue cryopreservation and autologous transplantation in preserving fertility and ovarian endocrine function in patients with cervical cancer. MethodsA 26-year-old patient with stage ⅡA1 cervical cancer underwent ovarian tissue harvesting and cryopreservation during cancer surgery. Following complete remission of the cancer， autologous ovarian tissue transplantation was performed. Follow-up monitoring included assessment of menopausal symptoms， hormone levels， and follicular development. ResultsSix months after transplantation， follicle-stimulating hormone levels decreased to 6.60 U/L， and estradiol levels increased from ＜10.00 ng/L to 89.00 ng/L. At 10 months after transplantation， ultrasound monitoring confirmed follicular development and physiological ovulation in the transplanted ovarian tissue. By 15 months after transplantation， follicle-stimulating hormone levels remained stable at 7.24 U/L， and estradiol levels further increased to 368.00 ng/L. Over 2 years after transplantation， the patient successfully gave birth to a healthy baby through assisted reproductive technology. ConclusionThe restoration of endocrine and ovulation functions in the transplanted cryopreserved ovarian tissue， followed by successful pregnancy， demonstrates the clinical success of ovarian tissue transplantation.

OBJECTIVE: To screen out the key metabolites related to diabetic foot (DF) by integrating genome-wide association studies (GWAS) and metabolome genome-wide association studies (mGWAS). METHODS: The literature databases such as PubMed and China national knowledge infrastructure(CNKI), as well as genomics databases such as PAN UKBB, FinnGen, and IEU Open GWAS were systematically retrieved from database estobilishment to November 2024 on DF-related single nucleotide polymorphisms and genome-wide association studies. DF-single nucleotide polymorphism-metabolite network was constructed by mGWAS package and mGWAS-Explorer platform. The causal relationship between key factors was evaluated by two-sample Mendelian randomization. The genetic correlation between DF and 575 metabolites (source:IEU Open GWAS) was evaluated by linkage disequilibrium score regression. In vitro experiments were conducted to induce injury of human umbilical vein endothelial cells with 30 mM glucose and intervene with 20 μM γ-tocopherol. Changes in cell migration, scratch healing and tube formation function were detected. RESULTS: Twenty-senen literatures on single nucleotide polymorphism literatures and 3 studies on GWAS were included. Genetic analysis results showed DF-related single nucleotide polymorphisms were enriched in vascular endothelial dysfunction-related pathways (such as fluid shear stress and atherosclerosis). The results of metabolic network analysis screened out 19 associated metabolites, among which 12 such as γ -tocopherol and pyruvate had significant genetic correlations with DF. Mendelian randomization suggested matrix metalloproteinase-9(MMP-9) might be a potential driver of DF (β=0.658, P=0.063 8), and the occurrence of DF could reduce the level of high-density lipoprotein (β=-0.002, P=0.015 2). The results of in vitro experiments confirmed that γ -tocopherol could improve endothelial dysfunction induced by high glucose, specifically manifested as an increase in the number of cell migrations, improvement in the scratch healing rate, and recovery of tubule formation ability (P<0.05). CONCLUSION DF has a genetic basis centered on vascular endothelial dysfunction, and its occurrence can lead to further metabolic disorders. The key single nucleotide polymorphism loci integrated provided molecular markers for the risk stratification of foot ulcers in diabetic patients. In addition, γ -tocopherol has demonstrated clinical application potential as a therapeutic drug for DF by significantly improving the function of vascular endothelial cells in a high-glucose environment.
Humans ; Diabetic Foot/drug therapy* ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Genomics ; Metabolomics ; Metabolome