OBJECTIVE To construct a risk prediction model for nonattainment plasma concentration of zonisamide in children with epilepsy， and to provide evidence for individualized dosing.METHODS Children with epilepsy who received standardized zonisamide treatment orally in Kunming Children’s Hospital were retrospectively selected as research subjects. Those treated from May 2022 to May 2024 were included in the modeling cohort， and those treated from June 2024 to January 2025 were included in the external validation cohort. According to plasma concentration， children were divided into therapeutic group and nonattainment group. Independent influencing factors for nonattainment plasma concentration of zonisamide were screened by collinearity diagnosis， univariate analysis， Lasso regression and random forest， based on which a nomogram risk prediction model was constructed and validated. Finally， the Shapley additive explanations （SHAP） method was used to interpret the features of the nomogram risk prediction model.RESULTS A total of 945 children with epilepsy were included in this study. There was no statistically significant difference in baseline data between the modeling cohort （531 cases） and the external validation cohort （414 cases） （ P ＞0.05）， indicating comparability. Through multi-stage feature screening， seven influencing factors were finally included to construct the prediction model， namely gender， age， dosage， aspartate transferase， total bilirubin， uric acid and vitamin D. The corrected area under the curve of the model was 0.799 in the modeling cohort and 0.762 in the external validation cohort， showing good calibration and clinical applicability. SHAP analysis showed that gender， dosage， total bilirubin， age and aspartate transferase were the top five important variables affecting model prediction.CONCLUSIONS The nomogram risk prediction model for nonattainment plasma concentration of zonisamide constructed in this study has stable predictive performance. Clinically， the risk of nonattainment plasma concentration can be quickly assessed by combining the child’s gender， age， dosage， liver and kidney function， and vitamin D， and the dosing regimen can be adjusted in time.

Objective To explore the communication preferences for advance care planning(ACP)among elderly hospitalized patients and to provide references for improving the ACP implementation rate.Methods Convenience sampling was used to select elderly hospitalized patients from a tertiary hospital in Wenzhou City between April and November 2023.Face-to-face surveys were conducted using a general data collection form and a self-designed questionnaire on ACP communication preferences.Mixed Logit Model,willingness-to-pay analysis,relative importance analysis,and subgroup analysis were employed to explore preferences.Results 204 questionnaires were distributed and 200 valid questionnaires were recovered,with a valid questionnaire response rate of 98.04％.The Mixed Logit Model analysis indicated that key attributes-communication timing,communication form,family participation in ACP communication,legal validity of ACP documents,and out-of-pocket costs-significantly influenced preferences(P＜0.05).Willingness-to-pay analysis showed that changes in communication timing,communication form,and family participation altered patients' willingness to pay.Relative importance analysis ranked the top 3 attributes as commu-nication timing,communication form,and family participation.Subgroup analysis revealed that gender,education level,and residence location affected preferences(P＜0.05).Conclusion Key attributes of ACP communication affect elderly hospitalized patients' preferences and willingness to pay,with variations across subgroups.Healthcare professionals should develop optimal communication programs based on patient preferences and individual characteristics.

Objective:To investigate the effect of protein tyrosine phosphatase D(PTPRD)demethylation on the proliferation,migration,and chemoresistance of gastric cancer(GC)cells through the phosphatidyl inositol 3 kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)pathway.Methods:The gastric cancer MKN-74 and MKN-45 cells,as well as human gastric mucosal epithelial GES-1 cells,GES-1 were cultured in vitro and PTPRD expression was detected.MKN-45 cells and their drug-resistant variant MKN-45/5-FU cells were routinely cultured and transfected with various vectors:PTPRD empty vector(NC group,NC/5-FU group),PTPRD overexpressing adenovirus(PTPRD group,PTPRD/5-FU group),shRNA empty vector(sh-NC group,sh-NC/5-FU group),shRNA PTPRD lentivirus(sh-PTPRD group,sh-PTPRD/5-FU group),and PTPRD overexpressing adenovirus+10 μmol/L 740Y-P treatment(PTPRD+740Y-P group,PTPRD+740Y-P/5-FU group).MTT assay and wound healing assay were used to assess cell proliferation and migration.Cell autophagy levels were assessed using autophagy assay,and the expression of epithelial-mesenchymal transition(EMT)and PI3K/Akt/mTOR pathway related proteins was detected using western blot(WB).MKN-45 cells were treated with 0,2.5,5,10,20 and 40 μmol/L 5-aza solutions,and the PTPRD mRNA expression and cell proliferation in MKN-45 cells were detected using qPCR and MTT assays.Results:PTPRD mRNA and protein were significantly downregulated in gastric cancer cells(P<0.05).Compared with the MKN-45 group,the numbers of autophagosomes and autophagosomes,as well as the protein expression of PTPRD,E-cadherin,and BAX significantly increased in the PTPRD group(all P<0.05),while cell proliferation,migration rate,and protein expression of p-PI3K,vimentin,p-Akt,and p-mTOR decreased significantly(all P<0.05);However,in the sh-PTPRD group,cell proliferation activity,migration rate,and protein expression of p-PI3K,vimentin,p-Akt,and p-mTOR increased notably,while the quantity of autophagosomes,autophagosomes,and protein expression of PTPRD,E-cadherin,and BAX decreased(all P<0.05).Compared with the PTPRD group,the PTPRD+740Y-P group showed an increase in cell proliferation activity,migration rate,protein expression of p-PI3K,vimentin,p-Akt,and p-mTOR(all P<0.05),and a decrease in number of autophagosomes,autophagosomes,and protein expression of PTPRD,E-cadherin,and BAX(all P<0.05).With the increase of 5-aza concentration,the mRNA expression of PTPRD in MKN-45 cells increased(P<0.05),while the cell proliferation activity decreased(P<0.05).Compared with the MKN-45/5-FU group,the cell migration rate and proliferation activity decreased in PTPRD/5-FU group,while the sh-PTPRD/5-FU group showed an increase in cell migration rate and proliferation activity(all P<0.05).Compared with the PTPRD/5-FU group,the PTPRD+740Y-P/5-FU group showed an increase in cell migration rate and proliferation activity(all P<0.05).Conclusion:PTPRD is downregulated in GC cells,and its demethylation may inhibit proliferation and migration of GC cells and enhance chemosensitivity by suppressing the PI3K/Akt/mTOR pathway.

Objective To explore the communication preferences for advance care planning(ACP)among elderly hospitalized patients and to provide references for improving the ACP implementation rate.Methods Convenience sampling was used to select elderly hospitalized patients from a tertiary hospital in Wenzhou City between April and November 2023.Face-to-face surveys were conducted using a general data collection form and a self-designed questionnaire on ACP communication preferences.Mixed Logit Model,willingness-to-pay analysis,relative importance analysis,and subgroup analysis were employed to explore preferences.Results 204 questionnaires were distributed and 200 valid questionnaires were recovered,with a valid questionnaire response rate of 98.04％.The Mixed Logit Model analysis indicated that key attributes-communication timing,communication form,family participation in ACP communication,legal validity of ACP documents,and out-of-pocket costs-significantly influenced preferences(P＜0.05).Willingness-to-pay analysis showed that changes in communication timing,communication form,and family participation altered patients' willingness to pay.Relative importance analysis ranked the top 3 attributes as commu-nication timing,communication form,and family participation.Subgroup analysis revealed that gender,education level,and residence location affected preferences(P＜0.05).Conclusion Key attributes of ACP communication affect elderly hospitalized patients' preferences and willingness to pay,with variations across subgroups.Healthcare professionals should develop optimal communication programs based on patient preferences and individual characteristics.

Objective:To explore the effect of the absent in melanoma 2 (AIM2) -mediated neuroinflammation in noise-induced cognitive dysfunction in rats.Methods:In April 2023, sixteen male Wistar rats were randomly divided into control group and noise group, with 8 rats in each group. The rats in the noise group were placed in 50 cm×50 cm×40 cm transparent boxes and exposed to 100 dB (A) white noise with a sound pressure level of 100 dB (A) (4 h/d for 30 d) . At the same time, rats in the control group were kept in similar boxes with environmental noise less than 60 dB (A) . After 30 days of noise exposure, the Morris water maze experiment was applied to test the learning and memory abilities of the rats; the pathological morphology of hippocampal tissues was observed by Hematoxylin-Eosin (HE) staining. Western blot was used to detect the protein expression levels of AIM2, cysteinyl aspartate specific proteinase-1 (caspase-1) , apoptosis-associated speck-like protein (ASC) , interleukin-1β (IL-1β) , IL-18, ionic calcium-binding articulation molecule-1 (Iba-1) , and glial fibrillary acidic protein (GFAP) . The expression of both Iba-1 and GFAP in hippocampal tissue was assessed by immunohistochemical staining. The co-localization of AIM2 with Iba-1 or GFAP was determined by immunofluorescence double staining.Results:Compared with the control group, the escape latency of rats in the noise group was increased by 16.29 s, 17.71 s, and 20.26 s on days 3, 4, and 5, respectively. On day 6, the noise-exposed rats spent shorter time in the target quadrant and had fewer times in crossing the platform[ (7.25±2.27) s and (1.13±0.64) times] than the control group[ (15.64±3.99) s and (4.25±2.12) times] ( P<0.05) . After noise exposure, hippocampal neurons of rats displayed marked nuclear hyperchromatic and pyknosis phenomenon. The noise-exposed rats had higher numbers of both microglia and astrocytes (27.00±2.65 and 43.33±5.51) in the DG area of the hippocampus relative to the control group (14.67±3.06 and 20.00±4.58) ( P<0.05) . Moreover, the glial cells in the noise group had larger cell cytosol with more and thicker branches. The protein expression levels of inflammatory cytokines Cleaved-IL-1β and Cleaved-IL-18 in the hippocampus of rats in the noise group (1.55±0.19 and 1.74±0.12) were significantly higher than the control group (1.00±0.11 and 1.00±0.13) ( P<0.05) . After noise exposure, the protein expression levels of AIM2, Cleaved-Caspase-1 and ASC (1.19±0.09, 1.34±0.07 and 1.14±0.01) were higher than the control group (1.00±0.07, 1.00±0.14 and 1.00±0.06) and differences between the two groups were statistically significant ( P<0.05) . A significant increase in the number of cells co-localizing AIM2 with Iba-1 or GFAP in the noise group (28.67±4.04 and 40.67±5.13) compared with the control group (15.67±4.04 and 17.67±3.79) , and statistically significant differences were observed between the two groups ( P<0.05) . Conclusion:Noise exposure may activate the AIM2 inflammasome in hippocampal glial cells of rats, releasing excessive inflammatory cytokines and causing neuroinflammation that damages neurons.

Objective:To explore the effect of the absent in melanoma 2 (AIM2) -mediated neuroinflammation in noise-induced cognitive dysfunction in rats.Methods:In April 2023, sixteen male Wistar rats were randomly divided into control group and noise group, with 8 rats in each group. The rats in the noise group were placed in 50 cm×50 cm×40 cm transparent boxes and exposed to 100 dB (A) white noise with a sound pressure level of 100 dB (A) (4 h/d for 30 d) . At the same time, rats in the control group were kept in similar boxes with environmental noise less than 60 dB (A) . After 30 days of noise exposure, the Morris water maze experiment was applied to test the learning and memory abilities of the rats; the pathological morphology of hippocampal tissues was observed by Hematoxylin-Eosin (HE) staining. Western blot was used to detect the protein expression levels of AIM2, cysteinyl aspartate specific proteinase-1 (caspase-1) , apoptosis-associated speck-like protein (ASC) , interleukin-1β (IL-1β) , IL-18, ionic calcium-binding articulation molecule-1 (Iba-1) , and glial fibrillary acidic protein (GFAP) . The expression of both Iba-1 and GFAP in hippocampal tissue was assessed by immunohistochemical staining. The co-localization of AIM2 with Iba-1 or GFAP was determined by immunofluorescence double staining.Results:Compared with the control group, the escape latency of rats in the noise group was increased by 16.29 s, 17.71 s, and 20.26 s on days 3, 4, and 5, respectively. On day 6, the noise-exposed rats spent shorter time in the target quadrant and had fewer times in crossing the platform[ (7.25±2.27) s and (1.13±0.64) times] than the control group[ (15.64±3.99) s and (4.25±2.12) times] ( P<0.05) . After noise exposure, hippocampal neurons of rats displayed marked nuclear hyperchromatic and pyknosis phenomenon. The noise-exposed rats had higher numbers of both microglia and astrocytes (27.00±2.65 and 43.33±5.51) in the DG area of the hippocampus relative to the control group (14.67±3.06 and 20.00±4.58) ( P<0.05) . Moreover, the glial cells in the noise group had larger cell cytosol with more and thicker branches. The protein expression levels of inflammatory cytokines Cleaved-IL-1β and Cleaved-IL-18 in the hippocampus of rats in the noise group (1.55±0.19 and 1.74±0.12) were significantly higher than the control group (1.00±0.11 and 1.00±0.13) ( P<0.05) . After noise exposure, the protein expression levels of AIM2, Cleaved-Caspase-1 and ASC (1.19±0.09, 1.34±0.07 and 1.14±0.01) were higher than the control group (1.00±0.07, 1.00±0.14 and 1.00±0.06) and differences between the two groups were statistically significant ( P<0.05) . A significant increase in the number of cells co-localizing AIM2 with Iba-1 or GFAP in the noise group (28.67±4.04 and 40.67±5.13) compared with the control group (15.67±4.04 and 17.67±3.79) , and statistically significant differences were observed between the two groups ( P<0.05) . Conclusion:Noise exposure may activate the AIM2 inflammasome in hippocampal glial cells of rats, releasing excessive inflammatory cytokines and causing neuroinflammation that damages neurons.

OBJECTIVE To investigate the efficacy and safety of clobazam in the additional treatment of refractory epilepsy in children， and provide reference for clinically safe and rational drug use. METHODS The literatures about additional clobazam treatment for refractory epilepsy in children were searched from PubMed， The Cochrane Library， Embase， CNKI， VIP and Wanfang database during the inception to November 2023. After literature screening and data extraction， the quality of included literature was evaluated according to quality evaluation tool for methodological evaluation indicators of non-randomized controlled trial， and then meta-analysis of single-group rate and sensitivity analysis were performed by using RevMan 5.3 software. RESULTS Finally， 18 one-arm studies were included， with a total of 1 424 children. The results showed that compared with before additional treatment， the proportion of patients with seizures-free （proportion of patients with seizure reduction of 100%） was 24%[95%CI （0.18，0.32）， P＜0.000 01] after conversion； the proportion of patients with seizure reduction ≥75% was 32%[95%CI（0.25，0.40）， P＜0.000 1] after conversion； the proportion of patients with seizure reduction ≥50% was 53%[95%CI（0.44，0.61），P＜0.000 01]； the proportion of patients with seizure reduction ＜50% or no change was 35%[95%CI（0.24，0.49），P＝0.04] after conversion； the proportion of patients with seizure increase was 9%[95%CI（0.05，0.18），P＜0.000 01] after conversion. The proportion of patients with adverse reactions was 31%[95%CI（0.23，0.40），P＜0.000 1] after conversion； the proportion of patients with discontinuation due to adverse reactions was 10%[95%CI（0.07， 0.15）， P＜0.000 01] after conversion. The common adverse drug reactions were drowsiness， fatigue and behavior change， etc. The results of the sensitivity analysis showed that the study was robust. CONCLUSIONS Clobazam is an effective additional therapy for refractory epilepsy in children， but its adverse effects should be vigilant.

Exposure to occupational noise and heavy metals are common occupational hazards in workplaces. Occupational noise exposure not only leads to noise-induced hearing loss but also cognitive dysfunction. Exposure to common heavy metals such as lead, manganese, and cadmium during work is closely related to cognitive dysfunction in workers. Combined exposure to noise and heavy metals is common in workplaces. However, current research on the combined effects of exposure to occupational noise with lead or manganese on workers' cognitive function is not comprehensive or systematic. The method for cognitive dysfunction identification varies, leading to a lack of comparability. And the causality between occupational exposure and cognitive dysfunction in workers has not been clarified. Therefore, studying the cognitive dysfunction due to combined exposure to noise and common heavy metals is of great significance for workers' occupational health. In the future, it is necessary to unify the method for cognitive dysfunction identification and conduct systematic and comprehensive research on the effects, mechanisms, and combined effects of exposure to occupational noise with lead, manganese, cadmium, and other heavy metals on workers' cognitive dysfunction, to ensure the occupational health rights and interests of workers.

Objective: To investigate the cognitive status of "living will" and "hospice care" among geriatrics students with different identities, and to provide a basis for improving teaching in corresponding sections of geriatric medicine. Methods:An online questionnaire was used to collect data from 426 students participating in specific courses in geriatric medicine and compare their differences in understanding of different issues. Results: There was no statistically significant difference in the understanding of the concept of "living will" among students with different identities (χ²=5.84, P=0.054). In terms of the concept of "hospice care" , geriatricians and general practitioners had a better understanding than that of medical undergraduates (χ²=37.932, P<0.001). Compared to geriatricians and medical undergraduates, general practitioners had a lower level of autonomy in deciding whether to use life support treatment, and the difference was statistically significant (χ²=28.737, P<0.001). There was a statistically significant difference between general practitioners and medical undergraduates in the understanding of "signing living will" (χ²=12.75, P=0.01). Conclusion: The promotion of "living will" and "hospice care" in humanities courses of medical undergraduate and continuing medical education needs to be strengthened, and the popularization and publicity among the general public should be enhanced to lay the groundwork for improving the quality of hospice care.

Public health emergencies not only bring great challenges to the conventional public health system, but also face some ethical dilemmas in the governance process. For example, the compulsory isolation measures affect the normal lives of some citizens, the normal medical treatment of non-epidemic patients may be constrained by complex governance environments, and the relationship between patient privacy protection and the public’s right to know needs to be deeply considered and balanced. To respond the ethical dilemmas in public health emergencies, it is necessary to explore more effective new ideas and methods under ethical concepts, combine with ethical needs in the governance of public health emergencies, comprehensively improve governance capabilities starting from the basic principles and behavioral standards of governance, with a view to providing more effective ethical support for the governance of public health emergencies.