Objective To explore the effect of different pontic designs in resisting stress interruption effect and roller coaster phenomenon through three-dimensional finite element analysis,providing clinical guidance for the application of clear aligners in extraction cases.Methods Four three-dimensional finite element models of different pontic designs in the extraction area of clear aligners were established,including the pontic-free connection design,the conventional hollow pontic design,the partially solid-filled pontic design and the fully solid-filled pontic design.All four aligner models were individually assembled with the dental arch model.A 0.2 mm distal movement of the canine was simulated to observe the initial displacement and periodontal ligament stress distribution of canine and second premolar in each group of models.Results The initial displacement tendency diagram revealed that in all experimental conditions,both the canine and second premolar exhibited tipping movement patterns.However,significant variations in initial displacement magnitudes were observed across different pontic designs.The fully solid-filled pontic-connected clear aligner model exhibited the greatest initial displacement values(both crown and root)and the maximum initial displacement magnitude.Notably,this kind of design displayed movement characteristics closer to bodily movement,indicating superior control efficacy in tooth positioning.Periodontal ligament stress analysis revealed that the fully solid-filled pontic-connected clear aligner model generated the highest maximum principal stress in the periodontal ligament.Conclusion This three-dimensional finite element study reveals that the application of solid-filled pontic in clear aligner therapy could improve biomechanical control at extraction sites by minimizing aligner distortion,reducing stress interruption effect and preventing the roller coaster phenomenon.

Objective:To investigate the patterns of mutation evolution in patients with acute myeloid leukemia (AML) during treatment and the possible clinical significances.Methods:A retrospective case series study was conducted. A total of 103 AML patients who were hospitalized at the Affiliated Yuebei People's Hospital of Medical College of Shantou University from November 2019 to August 2021 and underwent high-throughput next-generation sequencing (NGS) technology to detect the mutations of 128 AML-related genes in bone marrow samples were selected. Based on the NGS results, the somatic gene mutations in samples of patients collected at initial diagnosis (73 cases), complete remission (CR) (30 cases), non-remission (NR) (23 cases), and recurrence (12 cases) were analyzed, and the targeted drugs involved in the gene mutations detected in NR and recurrence samples were summarized.Results:The median age [ M ( Q1, Q3)] of onset for 103 patients was 58 (48, 66) years, including 64 males (61%) and 39 females (39%); 86 cases (83%) were primary AML, and 17 cases (17%) were secondary AML; at the initial diagnosis, 51 cases (50%) had normal karyotypes, 34 cases (33%) had abnormalities, and 18 cases (17.5%) were unknown. Compared with the CR samples, the mutation frequencies of FLT3 [29% (21/73) vs. 3% (1/30)], NPM1 [27% (20/73) vs. 3% (1/30)], NRAS [22% (16/73) vs. 3% (1/30)], and IDH2 [14% (10/73) vs. 0 (0/30)] were all higher in the initial diagnosis samples, and the differences were statistically significant (all P < 0.05); compared with the initial diagnosis sample, the median number of gene mutations in each CR sample was lower [4 (2, 5) vs. 7 (5, 9)], and the difference was statistically significant ( P < 0.001). However, there was no statistically significant difference in the median number of gene mutations in each patient between the initial diagnosis samples and the NR samples, the initial diagnosis samples and the recurrence samples, and the NR samples and the recurrence samples (all P > 0.05). Analysis of 14 patients with NGS data at initial diagnosis and CR showed that the same gene mutations could be detected at initial diagnosis and CR, such as DNAH23 (3 cases), USH2A (3 cases), etc; partial gene mutations were detected at initial diagnosis but were not detected at CR, including NRAS (5 cases), FLT3 (3 cases), ANKRD26 (3 cases), NPM1 (3 cases), ETV6 (3 cases), etc; ARID1B (1 case) and DNMT3A (1 case) were negative for mutations at initial diagnosis but positive upon reaching CR. Analysis of 14 patients with NGS data at initial diagnosis and NR showed that most gene mutations persisted at initial diagnosis and NR, such as DNMT3A (5 cases), NRAS (5 cases), KRAS (3 cases), RUNX1 (3 cases), etc; the mutant genes detected at initial diagnosis but not detected at NR included USH2A (2 cases), PCLO (2 cases), ATM (2 cases), FAT1 (2 cases), etc; partial gene mutations were not detected at initial diagnosis but were detected at NR, such as FAT1 (2 cases), TCF3 (2 cases), etc. Analysis of 5 patients with NGS data at CR and recurrence showed that some gene mutations were detected at both CR and recurrence, such as BCORL1 (1 case), ARID2 (1 case), SETD2 (1 case), VEGFC (1 case), etc; FLT1 (1 case) and GNAS (1 case) gene mutations were detected at CR but not detected at recurrence; at recurrence, some gene mutations that were not detected at CR were also detected, such as ANKRD26 (1 case), WT1 (1 case), etc. Among the 23 NR samples and 12 recurrence samples, the targets of drugs approved by US Food and Drug Administration or in clinical trials were detected in 14 (61%) and 5 (42%) samples respectively, including IDH1, IDH2, FLT3, KIT, KRAS, NRAS, SF3B1, U2AF1, and SRSF2. Conclusions:The number of gene mutations in AML patients during CR is significantly less than that at initial diagnosis, some gene mutations disappear when CR is achieved through treatment, but the majority of gene mutations persist during the treatment period, including NR and recurrence, suggesting that monitoring through NGS technology can help understand the evolution of gene mutations during AML treatment and discover the potential therapeutic targets.

Objective To explore the experiences of master degree nursing students and their supervisors under the dual-supervisor system.Methods A phenomenological research was adopted in this study eighteen master degree nursing students,five principle supervisors and four assistant supervisors from our university were selected through purposive sampling for semi-structured interviews between July and September 2023.Data acquired from the interviews was analysed using Colaizzi's method to summarise and extract the themes.Results Three main themes and eleven sub-themes were extracted,including the collaborative framework of the dual-mentor system(discrepancies in the perception of the dual-mentor system between faculty and students,the selection and matching process for associate mentors,the division of responsibilities and collaborative dynamics between primary and associate mentors,student-centered personalized training strategies,context-specific guidance provided by associate mentors,and the extent to which inter-role communication relies on student initiative),the benefits of the dual-mentor system(encompassing diversified academic and professional guidance,as well as integrated theoretical and practical support)and the expectations held by faculty and students regarding the dual-mentor system(refining institutional design and reinforcing accountability,enhancing the support infrastructure for associate mentors,and improving the tripartite communication mechanism among faculty,students,and associate mentors).Conclusion In nursing postgraduate education,the roles and responsibilities within the dual-mentor system can be more clearly delineated,and inter-mentor collaboration should be further strengthened.It is recommended to enhance tripartite communication among faculty,students,and associate mentors to foster the effective implementation and development of the dual-mentor system.

Objective To investigate the mechanism by which peripubertal exposure to di-2-ethylhexyl phthalate(DEHP)induces reproductive injury in adult male mice through impairment of Sertoli cell function and the blood-testis barrier.Methods A total of 180 male C57BL/6J mice(3 weeks old)were randomly divided into corn oil group(control group),and 5,25,125,250 and 500 mg/kg DEHP exposure groups.All groups received daily oral gavage for 5 consecutive weeks.Ten mice from each group were sacrificed for first material collection when they were 9 weeks old.The remaining F0 generation mice were mated with unexposed adult female mice at a male-to-female ratio of 1∶2 at 14 weeks of age for a period of 2 weeks.The second material collection was completed at 16 weeks of age,with 20 mice taken from each group.A computer-assisted analysis system was used to detect sperm density and motility in 9-week-old and 16-week-old male mice.The average birth body weight of F1 generation pups,survival rate of pups at 4 d after birth per litter,number of pups per litter,and male-to-female sex ratio within the litter were recorded.ELISA was used to detect hormone levels in the serum.Sperm abnormalities were observed using eosin staining.HE staining was used to observe pathological changes in testicular tissue.Immunofluorescence assay was utilized to detect the protein expression of tight junction protein 1(zonula occludens-1,ZO-1)and gap junction protein 43(connexin43,Cx43)related to the blood-testis barrier in testicular tissue,as well as the protein expression of apoptosis-related molecule Cleaved-Caspase3.Immunohistochemistry was used to detect the expression of Sertoli cell marker SOX9 protein in testicular tissue.TUNEL was used to detect apoptosis in testicular tissue.Comparative toxicogenomics database(CTD)was used to screen for mono-2-ethylhexyl phthalate(MEHP)induced reproductive damage-associated genes and combined with GO/KEGG and Reactome enrichment analysis to predict possible signaling pathways.An in vitro exposure model was established by treating TM4 cells with MEHP at concentrations of 0,50,100,200 and 400 μmol/L,respectively.CCK-8 assay,flow cytometry and Western blotting were applied to detect the cell viability,apoptosis,and protein expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2)and Bcl-2-associated X protein(Bax),and blood-testis barrier-related proteins ZO-1 and Cx43.Results Compared with the control group,the pregnancy rate was decreased from 80.0%to 52.5%,and the total number of pups was decreased from 212 to 125 in the female mice mating with the male from the 500 mg/kg group.Compared with the control group,the sperm density and motility were significantly reduced,and the total rate of sperm abnormalities was obviously increased in the 9-week-old DEHP-exposed mice(P<0.05),and even in the 16-week-old mice,the sperm motility was still in a dose-dependent downward trend(P<0.05).In the 25,125,250 and 500 mg/kg DEHP exposure groups,the thickness of the seminiferous epithelium was obviously decreased,with more cellular vacuolization and notable epithelial atrophy and degeneration.Cell apoptosis in the testicular tissue was enhanced,while the expression of ZO-1 and Cx43 were decreased in the 250 and 500 mg/kg exposure groups.The levels of androgen-binding protein,gonadotropin-releasing hormone,and testosterone in the serum were decreased in a dose-dependent manner(P<0.05),while those of luteinizing hormone and follicle-stimulating hormone showed a dose-dependent increase(P<0.05).Bioinformatics analysis showed that 153 genes related to male system diseases were screened out by CTD for MEHP.GO enrichment,KEGG pathway,and Reactome enrichment analyses displayed that the apoptosis signaling pathway was significantly enriched.CCK-8 assay showed that TM4 cell viability was decreased in a dose-dependent manner after MEHP treatment when compared with the control group(P<0.05).Western blotting indicated that MEHP treatment reduced the expression levels of Bcl-2,ZO-1 and Cx43(P<0.05),and enhanced that of Bax in comparison with the control group(P<0.05).Conclusion Peripubertal DEHP exposure may lead to reduced sperm quality and reproductive damage in adult male mice by disrupting the blood-testis barrier and activating Sertoli cell apoptosis.

Objective To analyze the current quality of treatment for hospitalized cancer patients in Bei-jing,identify major issues in treatment practices,and propose improvements.Methods Nine hospitals in Beijing were selected for examination.Expert on-site interviews and medical record sampling were conducted.The"Bei-jing Cancer Diagnosis and Treatment Quality Control Checklist"was used to assess the hardware,management,anti-cancer drug therapy,radiation therapy,and surgical treatment during cancer treatment at these hospitals from January to October 2023.The relevant problems were analyzed.Results Among the nine hospitals,two(22.2％)were equipped with laminar flow rooms,and three(33.3％)had intravenous drug preparation centers.In terms of institutional management,seven hospitals(77.8％)had standardized anti-cancer drug prescription authority management,eight(88.9％)had complete emergency plans,and five(55.6％)had oncology specialist pharmacists.Regarding anti-cancer drug therapy,the areas with higher completion rates included pathology diag-nosis support(97.6％),routine pre-treatment examinations(96.3％),adverse reaction evaluation(92.7％),discharge summaries(95.1％),and admission records(91.5％).However,the accuracy of tumor staging before treatment(70.7％)and the evaluation of therapeutic efficacy after drug treatment(76.9％)needed improvement.The oncology specialty significantly outperformed the non-oncology specialty in terms of the accuracy rate of TNM staging(86.0％vs.46.9％,P＜0.001),the completeness of informed consent forms(100％vs.68.8％,P＜0.001),the completeness of drug indication evaluation(96.0％vs.78.1％,P=0.025),the completeness of admission medical history records(98.0％vs.81.3％,P=0.008),the rationality of drug dosage(96.0％vs.75.0％,P=0.005),the rationality of drug infusion time(100％vs.62.5％,P＜0.001),and the rationality of the order of drug infusion(100％vs.87.5％,P=0.010).Although the quality of radiation therapy was high,the subsequent evaluation of therapeutic efficacy(39.3％)requires enhancement.In surgical treatment,the preoper-ative pathology diagnosis support rate(78.1％)and the accuracy of tumor staging(37.5％)were relatively low,indicating issues with incomplete preoperative evaluation and the absence of multidisciplinary discussions.Conclusions There remains significant room for improvement in the quality of cancer treatment in China.It is recommended to standardize tumor staging assessment processes,strengthen entry assessments for non-oncology departments,promote the implementation of multidisciplinary treatment models,and establish a multi-department collaborative management model.Continuous monitoring of cancer diagnosis and treatment quality indicators is es-sential to promote ongoing improvements in cancer treatment quality.

Eosinophilic gastroenteritis(EG)is a rare disease characterized by abnormal infiltration of eosinophils(Eos)in gastrointestinal tissues.Due to the unclear pathogenesis of EG and the lack of effective therapeutic drugs,research on its novel mechanisms,targets and drugs is critical.This article starts by outlining the research progress in the pathogenesis of EG,involving IgE mediated typeⅠimmediate allergic reactions and T helper 2 cell(Th2)mediated delayed allergic reactions.Then,the related targets of EG are summarized,including Th2 cytokines and factors regulating Eos function,but there has been no breakthrough in the treatment of these targets.Finally,the therapeutic drugs for EG are reviewed,such as glucocorticoids,antiallergic drugs and biologics.The advantages and disadvantages of various drugs are also described.However,these drugs cannot meet the current demands of clinical treatment and there is an urgent need to develop novel therapeutic drugs.It is believed that multi-target therapy is an ideal treatment for EG,and that traditional Chinese medicine and natural products should be the priorities of research and development for EG therapeutic drugs in the future.This review is expected to provide new ideas for the clinical treatment strategies and drug development of EG.

Objective:To describe the current status of responsive caregiving behavior of infant mothers,to analyze their influencing factors and pathways using the information-motivation-behavioral skills(IMB)model,and to provide a basis for further interventions related to responsive caregiving be-haviors and comprehensive promotion of early childhood development.Methods:This study was a cross-sectional survey using convenience sampling.Questionnaires were used to collect basic information about mothers and their infants,as well as data on mothers' responsive caregiving behavior,knowledge of re-sponsive caregiving,social support,and parenting self-efficacy.Multivariate linear regression models were employed to analyze the influencing factors of responsive caregiving behavior,and structural equa-tion modeling was used to analyze the pathways of these influencing factors.The criterion for inadequate responsive caregiving is defined as scores not exceeding the lower quartile(P25)of the total score.Results:Among 510 mothers of aged 0-12 months infants in Weifang City,the average score for respon-sive caregiving behavior was 16.41±3.99.The proportion of inadequate responsive caregiving was 25.7％.Mothers in the insufficient responsive caregiving group had lower scores in knowledge(7.70±1.41),social support(57.92±15.16),and parenting self-efficacy(30.36±6.48)compared with those in the sufficient group,with statistically significant differences(P＜0.001).Logistic regres-sion analysis indicated that the influencing factors for responsive caregiving included the level of know-ledge about responsive parenting[adjusted OR(aOR)=0.795,95％CI:0.566-0.838],social support(aOR=0.979,95％CI:0.961-0.996),and parenting self-efficacy(aOR=0.894,95％CI:0.857-0.932).Structural equation modeling revealed that knowledge of responsive caregiving(β=0.089,P=0.031),social support(β=0.153,P=0.001),and parenting self-efficacy(β=0.296,P＜0.001)were directly related to responsive caregiving behavior.Additionally,knowledge of responsive caregiving indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.095,P=0.014),and social support indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.497,P＜0.001).Conclusion:The current level of responsive caregiving behavior among mothers of 0-1-year-old infants in Weifang City is not satisfactory.Future development of responsive care-giving interventions should focus on providing caregivers with relevant knowledge of responsive caregiving based on their needs.Additionally,it is essential to offer social support from multiple aspects to enhance caregivers' parenting self-efficacy,thereby promoting improvements in responsive caregiving behavior.

Objective To Investigate the efficacy of modified electroconvulsive therapy(MECT)in patients with schizophrenia across different genders.Methods From May 2018 to August 2022,481 patients with schizophrenia were recruited from three psychiatric hospitals in Luzhou,Zigong,and Yibin.According to gender grouping,both groups received adjunctive MECT treatment for two consecutive weeks for a total of six treatments.The differences in positive and negative syndrome scale(PANSS)scores before and after treatment,UKU adverse reaction rating scale(UKU),and gastrointestinal symptom rating scale(GSRS)scores were compared between the two groups.Results After quality control,463 cases were followed up for analysis including 246 males and 217 females.Compared with pre-treatment,the total PANSS score and scores on each subscale were significantly reduced in both genders after treatment(P<0.001).When comparing the reduction rates between the groups,the male patients showed a higher reduction rate in negative symptoms than the female patients(31.24%±30.24%vs.25.80%±33.96%,P<0.05).However,there were no significant differences between the two groups in the reduction rates of the total score,positive symptoms,and general psychopathology(P>0.05).The comparison of adverse reactions showed that the frequency of other types of adverse reactions was higher in female patients than in male patients(47.47%vs.37.80%,P<0.05).However,no significant differences were observed in the adverse reactions related to the mental,neurological,autonomic nervous system,and gastrointestinal systems(P>0.05).Correlation analysis revealed that the reduction rate of the PANSS total score was positively correlated with smoking history(r=0.135,P=0.034)and alcohol history(r=0.160,P=0.012)in male patients,while the reduction rate of the PANSS total score was negatively correlated with the disease duration(r=-0.210,P=0.002)and positively correlated with the age of onset(r=0.145,P=0.032)in female patients.Conclusion MECT is significantly effective for both male and female patients with schizophrenia.Compared to female patients,MECT shows a more pronounced effect on negative symptoms in male patients.Additionally,the factors related to the efficacy of MECT differ between genders,indicating that it is necessary to consider the clinical characteristics of patients comprehensively when selecting an MECT treatment plan.

Objective To explore the effect of different pontic designs in resisting stress interruption effect and roller coaster phenomenon through three-dimensional finite element analysis,providing clinical guidance for the application of clear aligners in extraction cases.Methods Four three-dimensional finite element models of different pontic designs in the extraction area of clear aligners were established,including the pontic-free connection design,the conventional hollow pontic design,the partially solid-filled pontic design and the fully solid-filled pontic design.All four aligner models were individually assembled with the dental arch model.A 0.2 mm distal movement of the canine was simulated to observe the initial displacement and periodontal ligament stress distribution of canine and second premolar in each group of models.Results The initial displacement tendency diagram revealed that in all experimental conditions,both the canine and second premolar exhibited tipping movement patterns.However,significant variations in initial displacement magnitudes were observed across different pontic designs.The fully solid-filled pontic-connected clear aligner model exhibited the greatest initial displacement values(both crown and root)and the maximum initial displacement magnitude.Notably,this kind of design displayed movement characteristics closer to bodily movement,indicating superior control efficacy in tooth positioning.Periodontal ligament stress analysis revealed that the fully solid-filled pontic-connected clear aligner model generated the highest maximum principal stress in the periodontal ligament.Conclusion This three-dimensional finite element study reveals that the application of solid-filled pontic in clear aligner therapy could improve biomechanical control at extraction sites by minimizing aligner distortion,reducing stress interruption effect and preventing the roller coaster phenomenon.

Eosinophilic gastroenteritis(EG)is a rare disease characterized by abnormal infiltration of eosinophils(Eos)in gastrointestinal tissues.Due to the unclear pathogenesis of EG and the lack of effective therapeutic drugs,research on its novel mechanisms,targets and drugs is critical.This article starts by outlining the research progress in the pathogenesis of EG,involving IgE mediated typeⅠimmediate allergic reactions and T helper 2 cell(Th2)mediated delayed allergic reactions.Then,the related targets of EG are summarized,including Th2 cytokines and factors regulating Eos function,but there has been no breakthrough in the treatment of these targets.Finally,the therapeutic drugs for EG are reviewed,such as glucocorticoids,antiallergic drugs and biologics.The advantages and disadvantages of various drugs are also described.However,these drugs cannot meet the current demands of clinical treatment and there is an urgent need to develop novel therapeutic drugs.It is believed that multi-target therapy is an ideal treatment for EG,and that traditional Chinese medicine and natural products should be the priorities of research and development for EG therapeutic drugs in the future.This review is expected to provide new ideas for the clinical treatment strategies and drug development of EG.