OBJECTIVE To investigate the effect of pharmaceutical services guided by root cause analysis （RCA） in a problem-oriented manner combined with knowledge-attitude-practice （KAP） theory on reducing the incidence of protocol violations of investigational medicinal products in pediatric clinical trials. METHODS A total of 617 participants from 69 drug clinical trial projects conducted in our hospital from January 2016 to December 2020 were selected as the control group， and 868 participants from 72 drug clinical trial projects from January 2022 to December 2025 as the observation group. RCA was performed on the protocol violations of investigational medicinal product in the control group to identify the types and underlying causes. The control group received routine pharmaceutical services for drug clinical trials， while the observation group was provided with precision pharmaceutical services from the three dimensions of knowledge， attitude and practice on the basis of routine pharmaceutical services， according to the root causes identified by RCA. The occurrence of investigational medicinal products protocol violations was compared between the two groups. RESULTS The total incidence of protocol violations of investigational medicinal products， as well as the incidences of minor and major protocol violations， were all significantly lower in the observation group than in the control group （ P ＜0.001）. The main types of protocol violations in both groups included missed/under-/over-dosing of medications， non-adherence to administration time， failure to adjust dosage as required， and combined medication/vaccination in violation of the protocol. Regarding the responsible subjects of protocol violations， the incidences of protocol violations attributed to participants and their guardians as well as investigators and accidental factors were significantly lower in the observation group than in the control group （ P ＜0.001， P ＜0.001， P ＝0.025）. However， there were no statistically significant differences in the incidences of protocol violations caused by sponsor-related reasons between the two groups （ P ＞0.05）. CONCLUSIONS Pharmaceutical services led by pharmacists， based on problem-oriented RCA and combined with KAP theory， can effectively reduce the protocol violations of investigational medicinal products rate in pediatric clinical trials， thereby safeguarding the safety and rights of study participants.

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

OBJECTIVE To construct three-class （insufficient， normal， excessive） and two-class （insufficient， normal） models for predicting plasma concentration of valproic acid （VPA）， and compare the performance of these two models， with the aim of providing a reference for formulating clinical medication strategies. METHODS The clinical data of 480 patients who received VPA treatment and underwent blood concentration test at the Xi’an International Medical Center Hospital were collected from November 2022 to September 2024 （a total of 695 sets of data）. In this study， predictive models were constructed for target variables of three-class and two-class models. Feature ranking and selection were carried out using XGBoost scores. Twelve different machine learning algorithms were used for training and validation， and the performance of the models was evaluated using three indexes: accuracy， F1 score， and the area under the working characteristic curve of the subject （AUC）. RESULTS XGBoost feature importance scores revealed that in the three-class model， the importance ranking of kidney disease and electrolyte disorders was higher. However， in the two-class model， the importance ranking of these features significantly decreased， suggesting a close association with the excessive blood concentration of VPA. In the three-class model， Random Forest method performed best， with F1 score of 0.704 0 and AUC of 0.519 3 on the test set； while in the two-class model， CatBoost method performed optimally， with F1 score of 0.785 7 and AUC of 0.819 5 on the test set. CONCLUSIONS The constructed three-class model has the ability to predict excessive VPA blood concentration， but its prediction and model generalization abilities are poor； the constructed two-class model can only perform classification prediction for insufficient and normal blood concentration cases， but its model performance is stronger.

Background Enhancing the sense of honor and belonging among medical staff is a key component of establishing a modern hospital management system. Compared to medical staff at general hospitals, medical staff at oncology hospitals are more prone to job burnout, yet few studies in China have focused on job burnout among employees in oncology hospitals. Objective To propose a hypothetical model in which job well-being moderates the relationship between stressors and occupational burnout, to explore how stressors influence burnout and potential moderating role of job well-being, and to provide better understanding of job burnout and motivate employees based on the double-edge sword effect of stressors. Methods A cross-sectional survey was conducted in May 2022 at a tertiary oncology specialty hospital in Chongqing, China. A total of 1 898 medical staff were recruited. Data were collectedthrough four scales including a general information questionnaire, Maslach Burnout Inventory-Human Service Survey, Work Stressor Scale, and Occupational Well-being Scale for Medical Staff. Independent sample t-tests and one-way ANOVA were used for univariate comparisons of job burnout. Pearson correlation analysis was employed to examine the relationships between job burnout, stressors, and job well-being. Hierarchical linear regression was conducted to identify factors influencing job burnout and to examine potential moderating role of job well-being in the relationship between stressors and job burnout. Results A total of 2 123 questionnaires were distributed, with 1 898 valid responses, yielding an effective response rate of 89.4%. The prevalence of job burnout was 60.1%. The correlation coefficient was 0.717 (P<0.001) between stressors and burnout, −0.784 (P<0.05) between job well-being and burnout, and −0.744 (P<0.001) between stressors and job well-being. The quadratic stressors showed a statistically significant effect on burnout (β=0.404, P<0.01). Job well-being positively moderated the relationship between the linear stressors and burnout (β=1.289, P<0.001) and negatively moderated the relationship between the quadratic stressors and job burnout (β=−0.571, P<0.01), explaining 7.1% of the variance. Conclusion Job burnout prevalence is relatively high among employees in oncology hospitals. There is a curvilinear relationship between stressors and job burnout, with job well-being moderating this relationship. From a practical perspective, it is recommended to establish a tiered stress alert system to monitor employees’ stress levels and prevent prolonged exposure to high-pressure conditions. Additionally, improving employees’ job well-being through institutional incentives and developmental support can enhance its moderating role in mitigating the adverse effects of stressors on job burnout. Meanwhile, fostering coordinated responses between organizations and individuals is crucial for strengthening mental health management systems, thereby supporting a healthy, stable, and sustainable development of the healthcare workforce.

Objective: To examine the association between parent-child relationships and bullying behaviors among junior high school students, and to explore the moderating effect of community cohesion, so as to provide evidences for bullying intervention strategies. Methods: From November to December 2017, a cluster sampling method was used to survey 1 589 students in grades 6- 8 from three junior high schools in Jing an District,Shanghai. Anonymous electronic questionnaires collected data on parent-child relationships, community cohesion, and bullying behaviors. Multivariate Logistic regression analyzed the associations and moderation effects. Results: The prevalence of bullying behaviors among junior high school students was 7.80%. Spearman correlation analysis revealed negative associations between both parent-child relationships ( r =-0.13) and community cohesion ( r =-0.10) with bullying behaviors, while parent-child relationships positively correlated with community cohesion ( r =0.29) (all P <0.01). Junior high school students with positive parent-child relationships and higher perceived community cohesion showed lower risks of bullying behaviors ( OR=0.51, 95%CI =0.36-0.72; OR=0.58, 95%CI =0.45-0.76), with a significant interaction effect between the two factors (all P <0.05). Conclusions Positive parent-child relationships and community cohesion are negatively associated with bullying behaviors in middle school students. Supportive family relationships help reduce bullying, while stronger community cohesion enhances the protective effect of positive parent-child relationships against bullying.

Objective To examine the significance of susceptible gene detection for hereditary cancer syndrome (HCS) among general population. Methods A total of 2 928 individuals undergoing routine health examinations in Healthcare Center of Zhongshan Hospital, Fudan University, from September 2021 to April 2024 were enrolled retrospectively. Next generation sequencing was employed to identify susceptible genes for HCS. American College of Medical Genetics and Genomics (ACMG) guideline was used to analyze the pathogenicity of variants. Clinical data, imagings, follow-up data were also collected. Results The overall mutation rate of HCS panel was 3.59% (105/2 928), with 0.61% (18/2 928) for MutY DNA glycosylase (MUTYH), 0.27% (8/2 928) for breast cancer susceptibility gene 1/2 (BRCA1/2) and 0.23% (7/2 928) for mismatch repair (MMR) genes. Conclusions Healthy individuals carrying tumor susceptible genes usually lack the relevant clinical phenotypes. Whether comprehensive testing needs to be carried out among healthy people remains to be further explored.

Objective: To explore the association between parent-child connectedness and romantic relationships of secondary vocational school students and the moderating effect of peers romantic behavior, providing scientific basis for family and school health education. Methods: From March to April 2021，2 426 students from six secondary vocational and technical schools in Shanghai and Shaanxi Province were selected to conduct the survey by combining convenience sampling and cluster sampling.Electronic questionnaires were used to collect data on students family characteristics,oneself and peer romantic behaviors, and parent-child bonding. The t-test was employed for inter group comparisons, and binary Logistic regression analysis was conducted to examine the relationship between parent-child bonding levels, peer romantic behavior, and the romantic behavior of secondary vocational students. Results: The mother-child connection (2.63±0.77) was higher than that of father-child connection (2.48±0.78), with statistically significant difference ( t =6.83, P <0.01). Multivariable Logistic regression showed that overall father-child connectedness was negatively associated with students romantic relationships( OR =0.86，95% CI =0.76-0.97， P =0.02)and was only associated to girls romantic relationships when stratified by gender( OR =0.79，95% CI =0.66-0.93， P =0.01). Peers romantic relationships were positively associated with students romantic relationships ( OR =3.19-5.12, all P <0.01), and there was a moderating effect of the association between maternal connectedness and boys romantic relationships ( OR =1.67, 95% CI =1.05-2.66, P =0.03). Among boys without romantic peers, mother-child connectedness was negatively associated with their romantic relationships ( OR = 0.60 , 95% CI =0.36-0.99, P <0.05). In the total sample of Shanghai and girls of Shaanxi, father-child connectedness was negatively correlated with the romantic relationships of secondary vocational school students ( OR =0.84,0.65,95% CI =0.71-1.00,0.50-0.85,both P <0.05). Peer romantic relationships exhibited a negative moderating effect on the influence of mother-child connectedness on the romantic relationships of males in Shanghai ( OR =1.91, 95% CI =1.03-3.57, P <0.05). Conclusions The father-daughter connectedness is negatively correlated with girls romantic behavior, and peer romantic behavior weakens the correlation between mother-child connectedness and boys romantic behavior. Efforts should be made to enhance the parent-child connectedness of secondary vocational students and their ability to cope with peer influence, providing proper guidance for adolescents heterosexual interactions.

Objective:To investigate the drug resistance of newly diagnosed HIV-1 infected patients in Shanghai and to provide reference value for clinical antiretroviral therapy (ART).Methods:The peripheral venous blood plasma of 196 newly diagnosed HIV-1 infected patients screened according to the inclusion and exclusion criteria at the Shanghai Public Health Clinical Center from April to June 2023 was collected, HIV-1 RNA was extracted, the pol region was amplified by reverse transcription-polymerase chain reaction (RT-PCR) for sequencing, the mutation sites and ART drug resistance were analyzed.Results:The plasma of 196 newly diagnosed HIV-1 infected patients was amplified successfully in 162 cases (amplification success rate was 82.65%). The subtypes consisted of CRF07_BC(51.23%), CRF01_AE (27.78%), and others (6.79%), CRF55_01B (5.56%), B (3.70%), CRF01_AE/B (3.70%) and CRF08_BC (1.23%). The overall transmitted drug resistance rate was 7.41%, the protease inhibitors (PIs), non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (INSTIs) resistance rates were 3.09%, 3.70%, 0.00% and 0.62%, respectively. The proportion of NNRTIs-related mutation sites in B (66.67%) and CRF55_01B (88.89%) was higher than that in CRF07_BC (13.25%); the proportion of NNRTIs-related mutation sites in CRF55_01B (88.89%) was higher than that in CRF01_AE (22.22%) and other subtypes (18.18%), the difference was statistically significant (all P<0.05). Multivariate logistic regression analysis showed that the probability of PIs-related mutation sites in CRF01_AE/B was 21.71 times that of CRF07_BC[odds ratio ( OR)=21.71, 95% confidence interval ( CI): 3.36-140.27, P=0.001]. Conclusions:The transmitted drug resistance among newly diagnosed HIV-1 infected patients in Shanghai is at the moderate epidemic level, mainly NNRTIs and PIs-related drug resistance, and the INSTIs resistance rate is low, the use of INSTIs in ART regimens should be considered.

Objective:To investigate the short-term efficacy and safety of rituximab (RTX) in children with calcineurin inhibitor (CNI) resistant steroid resistant nephrotic syndrome (SRNS).Methods:A retrospective case analysis was conducted. Thirteen children with CNI resistant SRNS who were regularly treated with RTX (375 mg/m 2 per dose (maximum dose 500 mg), 1 dose per week, a total of 4 doses) in Department of Nephrology, Children′s Hospital of Fudan University from January 2016 to December 2023 were enrolled. The general data, disease related information, urinary protein/creatinine, serum albumin, blood creatinine before RTX treatment, immunosuppressants, adverse events, and monthly urinary protein/creatinine, serum albumin, and blood creatinine indexes within 6 months after RTX treatment were collected. The changes of urinary protein/creatinine, serum albumin and estimated glomerular filtration rate (eGFR) before and after RTX at 3 and 6 months were analyzed by using paired sample t test and Wilcoxon signed-rank test. Results:Among the 13 patients, 8 were male and 5 were female. The age of disease onset was 4.0 (2.9, 6.8) years and the age of RTX treatment was 9.8 (5.9, 13.6) years. There were 8 cases of focal segmental glomerulosclerosis, 3 cases of minimal change disease and 2 cases of mesangial proliferative glomerulonephritis. No clinically significant gene variation was detected in 12 cases and the other one did not receive gene test. Before RTX treatment, 11 cases were in chronic kidney disease stage G1, and 1 case each was in stage G2 and stage G3. Ten children completed 4 doses of RTX treatment, 1 patient completed 3 doses, and 2 patients completed 2 doses. Urinary protein/creatinine in 13 children at 3 and 6 months after RTX treatment was significantly lower than baseline (0.60 (0.13, 2.04), 0.49 (0.28, 1.10) vs. 1.44 (0.76, 4.11) mg/mg, Z=-2.34, -2.34, both P<0.05), and serum albumin was significantly higher than baseline ((35±8), (34±7) vs. (30±6) g/L, t=2.30, 2.60, both P<0.05). The eGFR at 6 months after RTX treatment was not significantly different from the baseline ((110±32) vs. (113±35) ml/(min·1.73 m 2), t=-0.76, P>0.05)). No serious adverse reactions occurred in this study. Conclusion:RTX could reduce urinary protein and increase serum albumin in short-term treatment in children with CNI resistant SRNS without significant side effects.

Objective To construct a health management information service platform for glaucoma patients to achieve continuous care.Methods The architecture of the health management information service platform for glaucoma patients was designed,and the platform was developed and implemented.Results A WeChat mini program-based health management information service platform was developed,consisting of a medical staff interface,a patient interface,and a backend management center.The platform integrates functions such as whole-process disease tracking,surgical management,medication and follow-up record-keeping with reminders,communication for follow-ups,and health education.From March 2021 to March 2024,the platform registered 2764 patients and 45 medical staff,with a total of 10 947 platform interactions.An overall assessment with the post-study system usability questionnaire yielded a mean score of 28.2,indicating good user experience.Conclusion This platform realizes closed-loop management for continuous care of glaucoma patients and provides a practical reference for the development and exploration of health management information service platforms.