Background Precise prevention and control refers to the means of dividing a large area into several small areas, clarifying the disease information in each small area, and carrying out prevention and control program in the small areas accordingly. It is an important starting point for a comprehensive prevention and control program targeting liver cancer, which can make the prevention and control of liver cancer more accurate and efficient. At present, most of the mainstream research on liver cancer prevention and control at home and abroad is only on the provincial and municipal level, which is difficult to meet the requirements of precise prevention and control. Objective Taking S County, a typical county in Central China as an example, to explore the temporal and spatial distribution of liver cancer and environmental health risks at the township scale, so as to provide scientific reference for developing precise prevention and control program. Methods Based on the liver cancer data in the tumor registry data and related environmental variables of S County from 2009 to 2018, a spatiotemporal analysis was carried out by using geographic information system mapping, global Moran index analysis, and cold and hot spot detection. The correlations between liver cancer and various environmental factors [fine particulate matter (PM_2.5), aerosol optical depth (AOD), temperature, precipitation, proportion of cultivated land, normalized difference vegetation index (NDVI), population density, and per capita gross domestic product (GDP)] in S County were preliminarily evaluated by using geodetectors. The environmental factors and their cumulative exposure years that were closely related to the liver cancer in S County were investigated by random forest model. On this basis, the towns were categorized based on total, age-specified, and gender-specified incidences of liver cancer through quartile ranking, and precise prevention and control suggestions were proposed. Results ZD, HD and BYJ had the highest incidence rates of liver cancer, and the average annual incidence rate was 628/10⁵, 58.28/10⁵, and 40.21/ 10⁵, respectively. In addition to the above three townships, LW was a high incidence area of liver cancer in male population and people under the age of 60 years, whose average annual incidence rate was 50.47/10⁵ and 10.59/10⁵, respectively, while LianC was a high incidence area of liver cancer in female population and people aged 60 years and above, whose average annual incidence was 23.39/10⁵ and 131.10/10⁵ respectively. The incidence of liver cancer was closely related to population density, GDP per capita, NDVI, and AOD, and their importance indicators were 0.92, 0.50, 0.43, and 0.36, respectively. The average time interval between continuous exposure to dangerous environmental factors and the diagnosis of liver cancer was 10 years. Conclusion HD, ZD, and BYJ of S County should vigorously carry out liver cancer screening, diagnosis, and treatment in the follow-up prevention and control, while HD and LW should continue to implement environmental protection. LW needs to strengthen the prevention and treatment of liver cancer in male population and population under 60 years old. LianC needs to strengthen the prevention and control of liver cancer in female population and people of and over 60 years of age. The towns around HD need to prevent the sudden outbreak of liver cancer. In addition, it is also necessary to strengthen the willingness of people in the county, especially those of and over 60 years old, to participate in liver cancer screening. This study provides important reference for the analysis of environmental health effects at a fine scale and for the prevention and control of liver cancer and environmental protection in different populations.

Periodontitis is a common oral disease caused by bacteria coupled with an excessive host immune response. Stem cell therapy can be a promising treatment strategy for periodontitis, but the relevant mechanism is complicated. This study aimed to explore the therapeutic potential of mitochondria from human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) for the treatment of periodontitis. The gingival tissues of periodontitis patients are characterized by abnormal mitochondrial structure. Human gingival fibroblasts (HGFs) were exposed to 5 μg/mL lipopolysaccharide (LPS) for 24 h to establish a cell injury model. When treated with hESC-MSCs or mitochondria derived from hESC-MSCs, HGFs showed reduced expression of inflammatory genes, increased adenosine triphosphate (ATP) level, decreased reactive oxygen species (ROS) production, and enhanced mitochondrial function compared to the control. The average efficiency of isolated mitochondrial transfer by hESC-MSCs was determined to be 8.93%. Besides, a therapy of local mitochondrial injection in mice with LPS-induced periodontitis showed a reduction in inflammatory gene expression, as well as an increase in both the mitochondrial number and the aspect ratio in gingival tissues. In conclusion, our results indicate that mitochondria derived from hESC-MSCs can reduce the inflammatory response and improve mitochondrial function in HGFs, suggesting that the transfer of mitochondria between hESC-MSCs and HGFs serves as a potential mechanism underlying the therapeutic effect of stem cells.
Humans ; Gingiva/cytology* ; Fibroblasts/metabolism* ; Mitochondria/physiology* ; Mesenchymal Stem Cells/cytology* ; Animals ; Periodontitis/therapy* ; Mice ; Reactive Oxygen Species/metabolism* ; Inflammation ; Lipopolysaccharides ; Human Embryonic Stem Cells/cytology* ; Cells, Cultured ; Adenosine Triphosphate/metabolism* ; Male

Objective:To investigate the potential characteristic manifestations and application value of the Dynamic Visual Acuity Test（DVAT） in vestibular migraine（VM）. Methods:A total of 50 VM patients（case group） and 50 healthy subjects（control group） diagnosed at the Department of Otorhinolaryngology Head and Neck Surgery, First Hospital of Shanxi Medical University between November 1, 2023, and December 31, 2024, were enrolled. The case group underwent DVAT, video head impulse test（vHIT）, caloric test, and Dizziness Handicap Inventory（DHI） assessment, whereas the control group only received DVAT. Group-based analyses were conducted to examine the effect of age on Dynamic Visual Acuity Loss（DVALoss）, as well as the correlations of DVALoss with vestibular function tests and DHI scores. Results:DVALoss in the case group was significantly higher than that in the control group（P<0.001）. In both groups, age was significantly and positively correlated with DVALoss（P<0.001）. Within the case group, DVALoss was strongly and positively correlated with DHI scores（r=0.807, P<0.001）; it was negatively correlated with the vestibulo-ocular reflex（VOR） gain in vHIT, though without clinical significance, and showed no significant association with the caloric test. Age and DVALoss collectively accounted for 71.3% of the variance in DHI scores（R²=0.713）, with age exerting a relatively minor actual impact. Conclusion:DVAT can sensitively identify the core functional impairments of VM. DVALoss, as a direct functional reflection of the pathological mechanism of VM, is strongly correlated with DHI scores. Incorporating DVALoss into standardized assessments may provide an objective basis for the diagnosis and management of VM.
Humans ; Migraine Disorders/diagnosis* ; Visual Acuity ; Case-Control Studies ; Head Impulse Test ; Vestibular Function Tests ; Female ; Male ; Adult ; Vestibular Diseases/physiopathology* ; Middle Aged ; Caloric Tests

Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity, expanding antibacterial spectra, and reducing required dosages. Previously, compound 15 was identified as a potential adjuvant for Polymyxin B (PB) against multidrug-resistant (MDR) Pseudomonas aeruginosa DK2; however, its clinical utility was hindered by high cytotoxicity, uncertain in vivo efficacy, and an unclear synergetic mechanism. To address these challenges, we synthesized and evaluated a series of novel benzamide derivatives, with A22 emerging as a particularly promising candidate. A22 demonstrated potent synergistic activity to PB, minimal cytotoxicity, improved water solubility, and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains. In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22. Moreover, A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2. Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production, reducing ATP levels, increasing NOX activity, and inhibiting biofilm formation, leading to bacterial death. These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants, offering a robust approach to combating MDR Gram-negative bacterial infections.

BACKGROUND:In the process of exploring the mechanism of Alzheimer's disease,the important role of bioinformatics for common target screening has been revealed,enabling the use of its screening results as a basis for exploring the therapeutic effects of drugs on the disease. OBJECTIVE:To predict the targets of liraglutide,a glucagon-like peptide-1 receptor agonist,in the treatment of Alzheimer's disease by bioinformatics and molecular biology. METHODS:DisGeNET database and SEA database were used to obtain the common genes of Alzheimer's disease and liraglutide.GO/KEGG enrichment analysis of common targets was conducted using DAVID online database.Protein-protein interaction networks were constructed using STRING database.The optimal dosage of liraglutide was determined using cell counting kit-8 assay.Expression of key proteins was analyzed using immunofluorescence and immunoblotting techniques.The mouse hippocampal neuron HT22 cell line was used for ex vivo experiments,and the cells were randomly divided into three groups:HT22 group,HT22+Aβ group,and HT22+Aβ+Lir group.No special treatment was done in the HT22 group,while Aβ1-42 was used to intervene in the HT22 cell line for 24 hours to construct an Aβ injury cell model in the HT22+Aβ group.In additional to modeling,liraglutide was added to the HT22+Aβ+Lir group for 12 hours. RESULTS AND CONCLUSION:A total of 3 333 genes associated with Alzheimer's disease were screened from DisGeNET database.Then 147 potential targets of liraglutide were obtained from SEA database.Finally,64 common targets of Alzheimer's disease and Liraglutide were determined using R packets.GO/KEGG analysis of common targets using DAVID online database suggested that common targets were mainly enriched in the following biological processes:neuroactive ligand-receptor interaction,renin-angiotensin system,bladder cancer,endopeptidase activity,peptide receptor activity,G protein-coupled peptide receptor activity,and transport vesicles.The obtained 64 common target proteins were imported into SRTING online database for protein-protein interaction network construction,and the top three genes,matrix metalloproteinases 2,9 and interleukin 1β,were obtained.The activity of cultured cells was detected by the cell counting kit-8 kit.Liraglutide at 100 nmol/L was the optimal concentration for antagonizing Aβ1-42.In the western blot and immunofluorescence assays,the expression of matrix metalloproteinases 2,9 and interleukin 1β was significantly increased in the HT22+Aβ group compared with the HT22 group(P＜0.05)but significantly decreased in the HT22+Aβ+Lir group compared with the HT22+Aβ group(P＜0.05).To conclude,the above bioinformatics data and secondary validation of differential genes in the GEO database suggest that both matrix metalloproteinases 2,9 and interleukin 1β could be potential targets of liraglutide in the treatment of Alzheimer's disease.

Objective To investigate the effects of long noncoding RNA(lncRNA)-NRON on apoptosis following myocardial infarc-tion(MI)in mice.Methods The C57BL/6 mice were randomly divided into four groups:sham operation(Sham)group,MI group,MI combined with lncRNA-NRON interference lentivirus(MI+shNRON)group,and MI combined with the negative control(NC)lentivirus(MI+NC)group.The expression of lncRNA-NRON was detected using real-time PCR.In addition,the pathology of the myocardial tissue injury was analyzed using HE staining,the myocardial infarction size was examined using TTC staining,and the extent of apoptosis was assessed using the TUNEL assay,respectively.The RPISeq database was used to predict the probability of interaction between lncR-NA-NRON and the voltage-dependent anionic channel protein(VDAC).The effect of lncRNA-NRON on the expression of VDAC protein was detected using Western blotting.Results The lncRNA-NRON expression was significantly increased in the MI group,and the tar-geted knockdown of lncRNA-NRON resulted in alleviation of the pathological myocardial tissue injury,reduction in the myocardial infarc-tion area,and inhibition of apoptosis.The probability of interaction between lncRNA-NRON and VDAC reached 0.9,indicating a high probability of their association.Additionally,lncRNA-NRON could regulate the protein expression of VDAC.Conclusion Knockdown of lncRNA-NRON could reduce the occurrence of myocardial injury following myocardial infarction.This effect may be attributable to a spe-cific mechanism wherein lncRNA-NRON affects the process of apoptosis by binding to VDAC,consequently suppressing its expression.

Objective:To investigate the role and underlying mechanisms of methyltransferase (Mettl) 3 in the process of angiotensin Ⅱ (Ang Ⅱ)-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis.Methods:C57BL/6J mice were used, in cell experiments, mouse renal pericytes were isolated and cultured using magnetic bead sorting. These pericytes were then induced to transdifferentiate into myofibroblasts with 1×10 6 mmol/L Ang Ⅱ, which was the Ang Ⅱ group, while pericytes cultured in normal conditions served as the control group. Successful transdifferentiation was verified by immunofluorescence staining, Western blotting, and real-time reverse transcription PCR (RT-qPCR) for α-smooth muscle actin (α-SMA). The levels of m6A modifications and related enzymes (Mettl3, Mettl14), Wilms tumor 1-associated protein (WTAP), fat mass and obesity protein (FTO), ALKBH5, YTHDF1, YTHDF2, YTHDC1, YTHDC2, YTHDC3 were assessed by Dot blot, RT-qPCR and Western blot. Mettl3 expression was inhibited in cells using lentivirus-mediated Mettl3-shRNA transfection, creating sh-Mettl3 and Ang Ⅱ+sh-Mettl3 groups, while lentivirus empty vector transfection served as the negative control (Ang Ⅱ+sh-NC group). The impact of Ang Ⅱ on pericyte transdifferentiation was observed, and the expression of downstream phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway proteins, including PI3K, AKT, phosphorylated AKT at serine 473 (p-AKT (S473)), and phosphorylated AKT at threonine 308 (p-AKT (T308)), were examined. PI3K gene transcription was inhibited by co-culturing cells with actinomycin D, and the half-life of PI3K mRNA was calculated by measuring residual PI3K mRNA expression over different co-culture time. The reversibility of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was assessed by adding the AKT activator SC79 to the Ang Ⅱ+sh-Mettl3 group. In animal experiments, mice were divided into these groups: sham group (administered 0.9% sterile saline), Ang Ⅱ group (infused with Ang Ⅱ solution), sh-Mettl3 group (injected with Mettl3 shRNA lentivirus solution), Ang Ⅱ+sh-Mettl3 group (infused with Ang Ⅱ solution and injected with Mettl3 shRNA lentivirus solution), and Ang Ⅱ+sh-Mettl3+SC79 group (administered Ang Ⅱ solution and Mettl3 shRNA lentivirus, with an additional injection of SC79). Each group consisted of six subject mice. Blood pressure was measured using the tail-cuff method before and after surgery, and serum creatinine, urea, and urinary albumin levels were determined 4 weeks post-surgery. Kidney tissues were collected at 28 days and stained using hematoxylin-eosin (HE) and Masson′s trichrome to assess the extent of renal fibrosis. Results:Primary renal pericytes were successfully obtained by magnetic bead sorting, and intervened with 1×10 6 mmol/L Ang Ⅱ for 48 hours to induce pericyte-to-myofibroblast transdifferentiation. Dot blot results indicated higher m6A modification levels in the Ang Ⅱ group compared to the control group ( P<0.05). RT-qPCR and Western blot results showed upregulation of Mettl3 mRNA and protein levels in the Ang Ⅱ group compared to the control group (both P<0.05). In the Ang Ⅱ+sh-Mettl3 group, Mettl3 protein expression was lower than that in the Ang Ⅱ group, with reduced expression levels of α-SMA, vimentin, desmin, fibroblast agonist protein (FAPa) and type Ⅰ collagen (all P<0.05). Compared to the control group, PI3K mRNA expression level was elevated in the Ang Ⅱ group, along with increased p-AKT (S473) and p-AKT (T308) expressions. In the Ang Ⅱ+sh-Mettl3 group, PI3K mRNA expression and p-AKT (S473) and p-AKT (T308) levels were decreased (all P<0.05). The half-life of PI3K mRNA was shorter in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ+sh-NC group (2.34 h vs. 3.42 h). The ameliorative effect of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was reversible by SC79. Animal experiments showed higher blood pressure, serum creatinine, urea, and 24-hour urinary protein levels, and a larger fibrosis area in the Ang Ⅱ group compared to the sham group (all P<0.05). The fibrosis area was smaller in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ group ( P<0.05), but increased again upon addition of SC79. Conclusion:Mettl3-mediated RNA m6A epigenetic regulation is involved in Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis, potentially by affecting PI3K stability and regulating the PI3K/AKT signaling pathway.

Objective:To explore the effectiveness of applying the ADDIE (analysis, design, develop, implement, evaluate) Model in clinical teaching for nursing interns in spine surgery department.Methods:Using a convenience sampling method, 44 nursing interns in the Department of Orthopedics at Peking Union Medical College Hospital were selected as the control group from July 2021 to May 2022, and were taught using traditional methods. From July 2022 to May 2023, 45 nursing interns were selected as the observation group, and a teaching team was formed to design a training program based on the five stages of the ADDIE instructional design model. This program was tailored to improve the overall clinical competence of the spinal surgery nursing interns. After training, the teaching effects were evaluated based on knowledge test scores, skills test scores, overall clinical competence, and teaching satisfaction.Results:After the training, the skills test scores in specialized nursing for the observation group were (94.87±1.10) points, higher than the control group's (93.98±1.41) points, with a statistically significant difference ( P<0.01). The observation group also scored higher than the control group in clinical judgment, organizational effectiveness, overall performance, and total score in the Mini-Clinical Evaluation Exercise, with statistically significant differences ( P<0.01). Additionally, the observation group reported higher satisfaction with the teaching plan and methods compared to the control group ( P<0.05) . Conclusions:Clinical teaching for spinal surgery nursing interns based on the ADDIE instructional design model can improve their specialized practical skills and overall clinical competence. The interns also expressed a high level of acceptance for this teaching design model.

Objective:To gain a deep understanding of the current cognition and training needs of nursing undergraduates regarding their emergency response teamwork skills, and to provide reference for the development of courses on emergency response teamwork among nursing undergraduates.Methods:From September to October 2023, purposive sampling was used to select 15 senior nursing undergraduates from Peking Union Medical College, Beijing University of Chinese Medicine, and Beijing City University as subjects for semi-structured interviews. Colazizzi 7-step analysis method was used to summarize and extract themes.Results:Three themes were extracted, including insufficient cognition and skill in emergency response, lack of emergency response teamwork cultivation, and the need for systematic and comprehensive training courses.Conclusions:Universities, hospitals, and other training institutions should work together to develop a systematic emergency response teamwork training course for nursing undergraduates, to cultivate the skills of nursing undergraduates and reserve talents for high-quality emergency response nursing teams.

Objective:To investigate the level of functional fitness of elderly hypertensive patients in the community and to analyze its influencing factors.Methods:A cross-sectional survey was used from November 2021 to September 2022, questionnaire survey and Senior Functional Fitness Test (SFT) were conducted on 189 elderly hypertensive patients in the community by convenience sampling method, multiple linear regression was used to analyze the influencing factors of SFT in elderly hypertensive patients in the community.Results:Totally 189 cases of community-aged hypertensive patients completed the investigation, 88 cases were male and 101 were female. The total SFT score of community-aged hypertensive patients was (58.61 ± 16.07). Single factor analysis showed that there were significant differences in SFT scores among patients with different gender, age and education ( t=-2.57, F=6.24, 7.54, all P<0.05). Multifactorial analysis revealed that age ( t=-5.55), gender ( t=2.63), and literacy ( t=5.69) were influential factors in the total SFT scores of community-dwelling elderly hypertensive patients (all P<0.05). Conclusions:Age, gender, and literacy level are the main factors affecting the total SFT scores of elderly hypertensive patients in the community, and community caregivers should pay close attention to the above elderly hypertensive population.