Objective To compare the clinical and cranial magnetic resonance imaging （MRI） features of neurological hepatolenticular degeneration （also known as Wilson disease，WD） with two different ATP7B gene mutations， and to investigate the association between the clinical and cranial MRI features in patients with the two mutation types of neurological WD. Methods The neurological WD patients with p.Arg778Leu or p.Pro992Leu homozygous mutation who were hospitalized in Affiliated Hospital of Neurology Institute， Anhui University of Chinese Medicine， from May 2014 to May 2025 were enrolled， and a retrospective analysis was performed for their demographic data， clinical manifestations， serological markers， and cranial MRI data to compare the differences between the two mutation types of neurological WD. Results A total of 103 neurological WD patients were enrolled， among whom there were 65 patients with p.Arg778Leu-mutant WD and 38 patients with p.Pro992Leu-mutant WD. There were no significant differences in demographics， clinical manifestations， and most serological markers between the two mutation types of WD， while there was a significant difference in cranial MRI findings between two groups， with significant differences in the damage of the thalamus （χ2=17.834，P<0.001），the midbrain （χ2=12.579， P<0.001）， and the pons （χ2=10.605， P=0.001） between the patients with p.Arg778Leu-mutant WD and those with p.Pro992Leu-mutant WD， and the multivariate analysis also showed significant differences in the above indicators （P<0.05）. Conclusion Demographic data， clinical manifestations， and serological markers are not associated with gene mutation types in neurological WD， while cranial MRI manifestations are associated with gene mutation types， among which p.Arg778Leu mutation of the ATP7B gene is more likely to involve the thalamus， the midbrain， and the pons.
Genotype

Objective:To explore the mediating effect of coping styles on the relationship between reinforce-ment sensitivity and non-suicidal self-injury(NSSI)behavior in adolescents.Methods:In total,4 462 middle school students were chosen by stratified cluster random sampling.All participants were asked with the question"In the past 1 year,have you intentionally harmed yourself(but not with the intention of ending your life)"to determine whether they had NSSI behavior in the past 12 months.All students were also assessed with the Trait Coping Style Questionnaire(TCSQ)and Reinforcement Sensitivity Scale(RSS).Results:The prevalence of NSSIbehavior in past year was 11.3％.Logistic regression analysis showed that the total scores of punishment sensitivity of RSS(OR=1.26,95％CI=1.10-1.46),negative coping style of TCSQ(OR=2.23,95％CI=1.92-2.60),and positive coping style of TCSQ(OR=0.70,95％CI=0.62-0.80)were associated with the screen-positive rate of NSSI behavior.Bootstrap test showed that the total scores of positive coping style of TCSQ(β=0.15,95％CI=0.10-0.20)and negative coping style of TCSQ(β=0.53,95％CI=0.43-0.64)partially mediated the relation-ship between the total scores of punishment sensitivity of RSS and the screen-positive rate of NSSI behavior in ado-lescents.Conclusion:The occurrence of NSSI behavior in adolescents is associated with the over-activation of pun-ishment sensitivity,partly through coping styles.

Objective To evaluate the practical application of the Media Fill Test(MFT)in assessing aseptic compounding competency of personnel in Pharmacy Intravenous Admixture Services(PIVAS).Methods A multicenter controlled study was conducted across six tertiary hospitals(center ①-⑥)in China.Participants were divided into an inexperienced group(Group A,n=118)and an experienced group(Group B,n=118),each performing five MFT operations.Positive controls validated medium efficacy.Contamination rates and pass rates were analyzed using chi-square and Fisher's exact tests.Results Valid samples included 584 for Group A and 588 for Group B.The sample pass rate was 66.78%(390/584)in Group A and 91.67%(539/588)in Group B,while personnel pass rates were 46.15%(54/117)and 80.51%(95/118),respectively,with significant intergroup differences(both P<0.01).All centers except Center ⑥ showed significantly higher pass rates in Group B(all P<0.05).Conclusion MFT effectively differentiates technical proficiency levels and is suitable for training evaluation of novice PIVAS staff.

Objective:To explore the mediating effect of coping styles on the relationship between reinforce-ment sensitivity and non-suicidal self-injury(NSSI)behavior in adolescents.Methods:In total,4 462 middle school students were chosen by stratified cluster random sampling.All participants were asked with the question"In the past 1 year,have you intentionally harmed yourself(but not with the intention of ending your life)"to determine whether they had NSSI behavior in the past 12 months.All students were also assessed with the Trait Coping Style Questionnaire(TCSQ)and Reinforcement Sensitivity Scale(RSS).Results:The prevalence of NSSIbehavior in past year was 11.3％.Logistic regression analysis showed that the total scores of punishment sensitivity of RSS(OR=1.26,95％CI=1.10-1.46),negative coping style of TCSQ(OR=2.23,95％CI=1.92-2.60),and positive coping style of TCSQ(OR=0.70,95％CI=0.62-0.80)were associated with the screen-positive rate of NSSI behavior.Bootstrap test showed that the total scores of positive coping style of TCSQ(β=0.15,95％CI=0.10-0.20)and negative coping style of TCSQ(β=0.53,95％CI=0.43-0.64)partially mediated the relation-ship between the total scores of punishment sensitivity of RSS and the screen-positive rate of NSSI behavior in ado-lescents.Conclusion:The occurrence of NSSI behavior in adolescents is associated with the over-activation of pun-ishment sensitivity,partly through coping styles.

Objective To evaluate the practical application of the Media Fill Test(MFT)in assessing aseptic compounding competency of personnel in Pharmacy Intravenous Admixture Services(PIVAS).Methods A multicenter controlled study was conducted across six tertiary hospitals(center ①-⑥)in China.Participants were divided into an inexperienced group(Group A,n=118)and an experienced group(Group B,n=118),each performing five MFT operations.Positive controls validated medium efficacy.Contamination rates and pass rates were analyzed using chi-square and Fisher's exact tests.Results Valid samples included 584 for Group A and 588 for Group B.The sample pass rate was 66.78%(390/584)in Group A and 91.67%(539/588)in Group B,while personnel pass rates were 46.15%(54/117)and 80.51%(95/118),respectively,with significant intergroup differences(both P<0.01).All centers except Center ⑥ showed significantly higher pass rates in Group B(all P<0.05).Conclusion MFT effectively differentiates technical proficiency levels and is suitable for training evaluation of novice PIVAS staff.

Oral submucous fibrosis(OSF)is a chronic and inflammatory mucosal disease caused by betel quid chewing,which belongs to oral potentially malignant disorders.Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development.The epithelium,which is the first line of defense against the external environment,can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment.However,the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear.In this study,we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes.MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts,where it promoted cell secretion,contraction,migration and fibrogenic marker(α-SMA and collagen type I)expression.The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1(TGFBR1)through the E3 ubiquitination ligase WWP1,thus facilitating downstream TGF-β pathway signaling.Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes.Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts.In conclusion,we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway,which provided a new perspective and strategy for the diagnosis and treatment of OSF.

Modified electroconvulsive therapy(MECT)has a good therapeutic effect on major depressive disorder(MDD),but its mechanism of action is still unclear.In recent years,accumulated studies have confirmed the effects of MECT on brain structure and function using neuroimaging techniques and large datasets obtained through global collaborations and the conclusions are becoming increasingly consistent.For example,there is an increase in gray matter volume in specific brain regions such as the hippocampus and amygdala,an increase in white matter microstructural integrity and normalization of brain functional connections associated with MDD,such as the hippocampus-amygdala-subgenual anterior cingulate cortex-prefrontal cortex network,hippocampus-thalamus-temporal cortex-parietal cortex network,etc.However,the relationship between these changes and the mechanism of MECT action still needs further investigation.This review provides an overview of the research progress on the structural and functional changes of the brain by MECT to provide methodological support and theoretical basis for its better application in clinical diagnosis and treatment.

Objective: To explore the mediating effect of parental hostile attribution bias on depression and anxiety between parents and children, so as to provide the reference for the promotion of children's mental health. Methods: Students of grades 2-6 in two public primary schools in Linping District, Hangzhou City and their parents were investigated using stratified sampling method in November 2022. Emotions of children were surveyed using Depression Self-Rating Scale for Child (DSRSC) and Screen for Child Anxiety Related Emotional Disorders (SCARED), while emotions and hostile attribution bias of parents were surveyed using Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS) and Social Cognitive Screening Questionnaire (SCSQ). Mediating effect of parental hostile attribution bias on depression and anxiety between parents and children was analyzed using a structural equation model. Results: Totally 300 questionnaires were allocated, and 263 valid questionnaires were recovered, with an effective rate of 87.67%. There were 137 boys (52.09%), and 126 girls (47.91%), with a mean age of (9.95±1.44) years. There were 69 fathers and 194 mothers investigated. The prevalence of depression among parents was 27.00%, the prevalence of anxiety among parents was 4.18%, and the median score of hostile attribution bias was 1.00 (interquartile range, 2.00). The prevalence of depression among children was 11.03%, and the prevalence of anxiety among children was 29.66%. Parents' depression and anxiety affected children's depression and anxiety directly (effect value=0.270, 95%CI: 0.131-0.436), and also indirectly affected children's depression and anxiety by increasing their hostile attribution bias (effect value=0.028, 95%CI: 0.004-0.082), with the mediating effect contributed 9.40% of the total effect. Conclusion Parents' depression and anxiety affect children's depression and anxiety directly or indirectly through hostile attribution bias.

Objective:To evaluate the robustness of fully automated adaptive planning for Ethos online adaptive radiotherapy (ART) based on the intelligent optimization engine (IOE).Methods:Clinical data of 11 stage ⅠB cervical cancer patients admitted to Peking Union Medical College Hospital between June 2021 and June 2022 were retrospectively analyzed. Original planning images and iterative cone-beam computed tomography (iCBCT) images of each radiotherapy treatment were acquired, and all patient data were imported into the Ethos simulator. IOE-based 9-field automatic plan generation was performed for 11 patients using Ethos, and the generated plans were sent to online adaptive radiotherapy simulation to obtain each online adaptive radiotherapy plan (273 fractions in total) and complete the simulated treatment. For comparison, manual plan design was performed based on the images and contoured structures used for online adaptive radiotherapy planning, and the manually plans created with evenly divided 9 fields. Dosimetric parameters, plan complexity parameters, and Mobius quality assurance (QA) pass rates were collected to compare and evaluate the robustness of the online adaptive radiotherapy plan in terms of organs at risk (OAR), target volume dosimetric parameters, and plan complexity by using paired t-test or rank sum test. Results:The online adaptive plan of cervical cancer had comparable planning target volume (PTV) coverage compared to the manual plan. For the clinical target volume (CTV) D 99%, online adaptive plan was significantly higher than the manual plan [(45.93±0.36) vs. (45.32±0.31) Gy, P<0.001]. For hot dose area, the maximum point dose (PTV D max) of adaptive plan was significantly higher than the manual plan [(49.89±1.25) vs. (48.48±0.77) Gy, P<0.001], but the PTV D 1% of adaptive plan was significantly lower than the manual plan [(47.22±0.29) vs. (47.59±0.48) Gy, P<0.001]. There was no statistical difference in the conformal index ( P=0.967). And there was significant difference in the homogeneity index, with same medians and less dispersion in adaptive plan ( P<0.001). For OAR dose, bladder D mean, rectal V 40 Gy, small intestine D mean of adaptive plan was slightly higher than that of the manual plan; the rectal D mean, small intestine D 2 cm3 of the adaptive plan was slightly lower than that of manual plan; dosimetric parameters of right and left femoral heads, spinal cord and bone marrow of the adaptive plan were better than those of manual plan. The adaptive plan had more monitor units (MU) than the manual plan, but the complexity of the adaptive plan was significantly lower than that of the manual plan (0.135±0.012 vs. 0.151±0.015, P<0.001). For Mobius γ pass rate (5%/3 mm), both adaptive and manual plans met clinical requirements. Conclusion:Ethos cervical cancer online adaptive plan, which is based on the IOE engine, demonstrates good robustness and ensures the quality of online adaptive plans generated for each treatment fraction.

Objective:To evaluate the automatic optimization performance and clinical feasibility of the intelligent optimization engine (IOE) in the Ethos online adaptive radiotherapy platform.Methods:Clinical data of 11 patients with postoperative cervical cancer treated with Halcyon accelerator were retrospectively analyzed. Manual planning was performed for all patients using the 4 full arc volumetric modulated arc therapy (VMAT) (Manual-4Arc) in Eclipse, with a prescription dose of 45 Gy/25F. Patient images and structures were imported into the Ethos simulator, and appropriate clinical goals were added based on clinical requirements. The target coverage was normalized to 95%. Automatic plan generation was conducted using IOE, resulting in 7, 9, and 12 field intensity modulated radiotherapy (IMRT) plans (IMRT-7F、IMRT-9F、IMRT-12F), as well as 2 and 3 arc VMAT plans (VMAT-2Arc、VMAT-3Arc). Dosimetric index comparisons were made between the Manual-4Arc plans and the 5 groups of IOE-generated plans through one-way analysis of variance. Based on the analysis results, Turky post hoc multiple comparisons were performed to evaluate the automatic optimization performance of IOE.Results:In terms of the high dose area, the IMRT-12F plans showed the lowest D 1% for the planning target volume (PTV), and there were significant differences compared to the Manual-4Arc plans ( P=0.004). Regarding target coverage, all groups produced clinical target volume (CTV) plans that met the clinical requirements. Although the Ethos online adaptive plans were normalized during planning, the PTV coverage was slightly insufficient. For organs at risk (OAR) close to the target, such as the bladder, there were significant differences in V 30 Gy, V 40 Gy, and D mean among the 6 groups of plans. The dose ranking for the bladder was generally as follows: IMRT-12F