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.

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 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.

Objective:To explore the effectiveness of limb motor rehabilitation program based on patient health engagement (PHE) model in patients with hemorrhagic stroke, and to provide reference for the limb motor rehabilitation management of hemorrhagic stroke patients.Methods:Through literature review and Delphi expert correspondence, a limb motor rehabilitation program for hemorrhagic stroke patients based on the PHE model was constructed. A non-contemporaneous controlled study was conducted, 45 hemorrhagic stroke patients hospitalized in the Department of Neurosurgery of Shanxi Bethune Hospital from March to August 2022 were selected by convenience sampling method as the control group, and routine exercise rehabilitation measure was given, 45 hemorrhagic stroke patients from September 2022 to February 2023 were selected as the intervention group, a limb motor rehabilitation program based on PHE model was implemented on the basis of control group. The functional exercise compliance, limb motor function, daily activity ability, emotional and social dysfunction of patients in the two groups were observed before intervention, 1 and 3 months after intervention respectively.Results:A total of 85 patients with hemorrhagic stroke were included. There were 42 patients in the intervention group, 25 males and 17 females, aged (52.07 ± 9.91) years old, and 43 patients in the control group, 21 males and 22 females, aged (53.93 ± 10.52) years old. There were no significant differences in the functional exercise compliance, limb motor function, daily activity ability, emotional and social dysfunction of patients before intervention between the two groups. At 3 months after intervention, the functional exercise compliance score in the intervention group was (40.83 ± 7.92) points, higher than that in the control group (37.14 ± 6.44) points, and the difference was statistically significant ( t = 2.36, P<0.05). At 1 and 3 months after intervention, the scores of limb motor function and daily activity ability in the intervention group were (27.12 ± 6.74), (33.67 ± 6.54) points and (61.31 ± 6.72), (74.40 ± 8.71) points, which were higher than (24.91 ± 6.03), (27.02 ± 6.59) points and (52.33 ± 9.78), (60.12 ± 10.03) points of the control group, the differences were statistically significant ( t values were 2.06-7.01, all P<0.05), the scores of emotional and social dysfunction were (75.52 ± 22.09) and (58.33 ± 18.88) points, which were lower than (86.02 ± 23.04), (78.51 ± 21.67) points of the control group, and the differences were statistically significant ( t = - 2.14, - 4.57, both P<0.05). Conclusions:The limb motor rehabilitation program based on the PHE model could improve the exercise compliance of patients with hemorrhagic stroke, improve the limb motor function and daily activity ability of patients, alleviate negative emotions, and reduce the level of social dysfunction.

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 further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

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 effect of T cell immunoreceptor with Ig and ITIM domains (TIGIT) on the function of CD8⁺ T cells in the lungs of Plasmodium infected mice. Methods The lungs of the mice infected with Plasmodium yoelii were isolated, weighed and photographed after 12 days' infection. After dissolution, lung lymphocytes were isolated, counted and stained, and then the contents of CD8⁺ and TIGIT⁺CD8⁺ T cells were detected by flow cytometry. The expressions of L selectin (CD62L), CD69, programmed death 1 (PD-1), CD25, and C-X3-C motif chemokine receptor 1 (CX3CR1) on TIGIT⁺CD8⁺ T cells were detected by flow cytometry. After stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, the ability of TIGIT⁺CD8⁺T cells to secrete interferon γ(IFN-γ), interleukin 21 (IL-21), IL-4, IL-17, and IL-10 was detected. Results The body mass of mice with Plasmodium infection was reduced. The lungs became darker, and the ratio of the lung mass to body mass was significantly increased. Compared with the normal mice, the percentages and absolute quantity of CD8⁺ and TIGIT⁺CD8⁺ T cells in the lungs of the infected mice were significantly increased. The percentage of TIGIT⁺CD8⁺ T cells expressing CD62L in the infected group was significantly lower, while the percentage of the CD69, PD-1, and CX3CR1 cells were significantly higher than that of TIGIT⁺CD8⁺ T cells from the normal mice. The percentages of TIGIT⁺CD8⁺ T cells secreting IL-21, IL-4, IL-17 and IL-10 cells in the infected group were significantly lower. Conclusion The lung lesions from mice with Plasmodium infection are obvious, the numbers of TIGIT⁺CD8⁺ T cells increase, and these cells express a variety of activation-related molecules, but the ability to secrete cytokines is reduced.
Animals ; Mice ; CD8-Positive T-Lymphocytes ; Cytokines/metabolism* ; Interferon-gamma/metabolism* ; Interleukin-10/metabolism* ; Interleukin-17/metabolism* ; Interleukin-4/metabolism* ; Lung/metabolism* ; Malaria/metabolism* ; Plasmodium yoelii/metabolism* ; Programmed Cell Death 1 Receptor/metabolism*