There is a substantial unmet need for treatments in the field of pediatric rare diseases, and investigator initiated trial(IIT) provide a critical pathway for testing and developing new drugs or treatment strategies. However, healthcare institutions, when conducting such research, must address compliance risks related to project approval, contract management, data protection, and conflict of interest management. This study aims to analyze the particularities and challenges of IIT in pediatric rare diseases, review relevant regulations and regulatory requirements, and provide healthcare institutions with a reference framework for compliance risk management to maximize the benefits of IIT. Based on literature review, analysis of laws and regulations, practical work experience, and frameworks from other institutions, we summarize the unique aspects of pediatric rare disease IIT in terms of participant characteristics, innovative technologies, and organizational structures.On this basis, targeted compliance management recommendations are proposed, which include establishing a risk rating and full-cycle risk monitoring mechanism, a consent and ethical review mechanism tailored to pediatric participants, a robust contract management mechanism, a comprehensive data security management mechanism, and a multidisciplinary team and multi-channel compensation mechanism. The study concludes that healthcare institutions, funders, and other collaborating entities should implement compliance management in line with the characteristics of IIT to ensure the safety and effectiveness of research and facilitate innovation and development in the treatment of pediatric rare diseases.

OBJECTIVE To study the pharmacokinetic characteristics of ciprofol in pregnant and fetal rats， and provide reference for the application of ciprofol in cesarean section. METHODS Eight pregnant rats were selected. A single dose of 2.4 mg/kg of ciprofol was administered via the tail vein. One fetal rat was selected at 2， 4， 8， 12， 16， 25， 35， 45， 60， and 90 minutes respectively after ciprofol administration. Subsequently， whole blood samples were collected simultaneously from both the pregnant rats and fetal rats. HPLC-MS/MS method was used to determine the concentration of ciprofol in the bodies of pregnant and fetal rats. The ratios of fetal-to-maternal blood concentrations （F/M ratios） at each time point were calculated， and the F/M-time curves were plotted. Subsequently， non-compartmental pharmacokinetic parameters were computed using DAS 2.0 software. RESULTS Compared with pregnant rats， cmax， AUC0-90 min and AUC0-∞ of ciprofol in fetal rats were decreased significantly， while MRT was increased significantly （P＜0.05）. The F/M curve of ciprofol initially increased and then decreased， and between 0.16- 0.84， reaching a maximum value of 0.84 at 45 minutes. CONCLUSIONS Ciprofol can penetrate the placental barrier， and there are significant differences in pharmacokinetic parameters between pregnant and fetal rats. Moreover， the exposure level of ciprofol in fetal rats is much lower than that in pregnant rats. Therefore， ciprofol shows promise as an ideal anesthetic agent for cesarean section delivery.

OBJECTIVE To investigate the impact of Netupitant and palonosetron hydrochloride capsules （NEPA） on the pharmacokinetics of Paclitaxel for injection （albumin bound） （i. e. albumin-bound paclitaxel） under different intestinal microenvironment conditions. METHODS Male SD rats were divided into a normal group and a model group （n＝16）. Rats in the model group were intragastrically administered vancomycin solution to establish an intestinal disorder model. The next day after modeling， intestinal microbiota diversity was analyzed， and the mRNA expressions of cytochrome P450 3A1 （CYP3A1） and CYP2C11 in small intestine and liver tissues as well as those protein expressions in liver tissue were measured. Male SD rats were grouped as described above （n＝16）. The normal group was subdivided into the TP chemotherapy group （TP-1 group） and the TP chemotherapy+NEPA group （TP+NEPA-1 group）； the model group was subdivided into the TP chemotherapy group （TP-2 group） and the TP chemotherapy+NEPA group （TP+NEPA-2 group） （n＝8）. Rats in the TP+NEPA-1 and TP+NEPA-2 groups received a single intragastric dose of NEPA suspension （25.8 mg/kg， calculated by netupitant）. One hour later， all four groups received a single tail vein injection of albumin-bound paclitaxel and cisplatin. Blood samples were collected at different time points after the last administration. Using azithromycin as the internal standard， plasma paclitaxel concentrations were determined by liquid chromatography-tandem mass spectrometry. The main pharmacokinetic parameters were calculated using DAS 2.0 software and compared between groups. RESULTS Compared with the normal group， the model group showed significantly decreased Chao1 and Shannon indexes （P＜0.05）， significant alterations in microbiota composition and relative abundance， and significantly downregulated expressions of CYP3A1 mRNA in liver tissue and CYP2C11 mRNA in both small intestine and liver tissues （P＜0.05）. Compared with the TP-1 group， the AUC0－t， AUC0－∞， MRT0－t of paclitaxel in the TP-2 group， the cmax， AUC0－t， AUC0－∞ of paclitaxel in the TP+NEPA-1 group and TP+NEPA-2 group were significantly increased or prolonged； CL of paclitaxel in the TP-2 group， Vd and CL of paclitaxel in the TP+NEPA-1 group and the TP+NEPA-2 group were significantly decreased or shortened （P＜0.05）. Compared with the TP-2 group， cmax of paclitaxel in the TP+NEPA-2 group was significantly increased， and Vd and MRT0－t were significantly decreased or shortened （P＜0.05）. CONCLUSIONS Intestinal microbiota disorder affects the mRNA expressions of CYP3A1 and CYP2C11， leading to decreased clearance and increased systemic exposure of paclitaxel. Concomitant administration of NEPA under normal intestinal microbiota condition increases paclitaxel exposure. However， under conditions of intestinal microbiota disorder， concomitant administration of NEPA has a limited impact on paclitaxel systemic exposure.

Objective To predict the lymph node metastasis status of patients with invasive pulmonary adenocarcinoma by constructing machine learning models based on primary tumor radiomics, peritumoral radiomics, and habitat radiomics, and to evaluate the predictive performance and generalization ability of different imaging features. Methods A retrospective analysis was performed on the clinical data of 1 263 patients with invasive pulmonary adenocarcinoma who underwent surgery at the Department of Thoracic Surgery, Jiangsu Province Hospital, from 2016 to 2019. Habitat regions were delineated by applying K-means clustering (average cluster number of 2) to the grayscale values of CT images. The peritumoral region was defined as a uniformly expanded area of 3 mm around the primary tumor. The primary tumor region was automatically segmented using V-net combined with manual correction and annotation. Subsequently, radiomics features were extracted based on these regions, and stacked machine learning models were constructed. Model performance was evaluated on the training, testing, and internal validation sets using the area under the receiver operating characteristic curve (AUC), F1 score, recall, and precision. Results After excluding patients who did not meet the screening criteria, a total of 651 patients were included. The training set consisted of 468 patients (181 males, 287 females) with an average age of (58.39±11.23) years, ranging from 29 to 78 years, the testing set included 140 patients (56 males, 84 females) with an average age of (58.81±10.70) years, ranging from 34 to 82 years, and the internal validation set comprised 43 patients (14 males, 29 females) with an average age of (60.16±10.68) years, ranging from 29 to 78 years. Although the habitat radiomics model did not show the optimal performance in the training set, it exhibited superior performance in the internal validation set, with an AUC of 0.952 [95%CI (0.87, 1.00)], an F1 score of 84.62%, and a precision-recall AUC of 0.892, outperforming the models based on the primary tumor and peritumoral regions. Conclusion The model constructed based on habitat radiomics demonstrated superior performance in the internal validation set, suggesting its potential for better generalization ability and clinical application in predicting lymph node metastasis status in pulmonary adenocarcinoma.

Fanconi anemia (FA) is an inheritable disorder that presents with bone marrow failure, developmental anomalies, and an increased susceptibility to cancer. The etiology of this condition stems from a genetic mutation that disrupts the proper repair of interstrand DNA cross-links (ICLs). The resultant dysregulation of the DNA damage response mechanism can induce genomic instability, thereby elevating the mutation rates and the likelihood of developing cancer. The FA pathway assumes a pivotal role in safeguarding genome stability through its involvement in the repair of DNA cross-links and the maintenance of overall genomic integrity. A mutation in the germ line of any of the genes responsible for encoding the FA protein results in the development of FA. The prevalence of aberrant FA gene expression in somatic cancer, coupled with the identification of a connection between FA pathway activation and resistance to chemotherapy, has solidified the correlation between the FA pathway and cancer. Consequently, targeted therapies that exploit FA pathway gene abnormalities are being progressively developed and implemented. This review critically examines the involvement of the FA protein in the repair of ICLs, the regulation of the FA signaling network, and its implications in cancer pathogenesis and prognosis. Additionally, it explores the potential utility of small-molecule inhibitors that target the FA pathway.

ObjectiveTo assess the microstructural involvement of gray matter in recovered COVID-19 patients using Synthetic MRI. MethodsThis study was conducted in 29 recovered COVID-19 patients， including severe group （SG， n=11） and ordinary group （OG， n=18）. Healthy volunteers matched by age， sex， BMI and years of education were selected as a healthy control group （HC=23 cases）. Each subject underwent synthetic MRI to generate quantitative T₁ and T₂ maps， and the T₁ and T₂ maps were segmented into 90 regions of interest （ROIs） using automatic anatomical labeling （AAL） mapping. T₁ and T₂ values for each ROI were obtained by averaging all voxels within the ROIs. The T₁ and T₂ values of the 90 brain regions between the three groups were compared. ResultsRelative to HC， the SG had significantly higher T2 values in bilateral orbital superior frontal gyrus， bilateral parahippocampal gyrus， bilateral putamen， bilateral middle temporal gyrus， bilateral Inferior temporal gyrus， left orbital superior frontal gyrus， left orbital inferior frontal gyrus， left gyrus rectus， left anterior cingulate and paracingulate gyri， right median cingulate and paracingulate gyri， left posterior cingulate gyrus， and left supramarginal gyrus （P＜0.05）； Relative to OG， SG showed significantly increased T₂ values in the left rectus gyrus， left parahippocampal gyrus， bilateral middle temporal gyrus， and bilateral inferior temporal gyrus （P＜0.05）. Relative to HC， the T₁ values of SG were significantly increased in bilateral orbital superior frontal gyrus， left rectus gyrus， left anterior cingulate and paracingulate gyri， right posterior cingulate gyrus， left parahippocampal gyrus， left lingual gyrus， left putamen， left thalamus（P＜0.05）； Relative to OG， the T₁ values of SG were significantly higher in the right posterior cingulate gyrus， right calcarine fissure and surrounding cortex， and left putamen （P＜0.05）. ConclusionsEven after recovering from COVID-19， patients may still have persistent or delayed damage to their brain gray matter structure， which is correlated with the severity of the condition. SyMRI can serve as a sensitive tool to assess the extent of microstructural damage to the central nervous system， aiding in early diagnosis of the disease.

Objective: To investigate the correlation between campus bullying and suicidal tendency symptoms comorbidity with addictive behavior among middle and high school students in Hainan Province, so as to provide a theoretical basis for health education and behavioral intervention in schools. Methods: In July 2023, an anonymous questionnaire survey was conducted among 6 654 middle and high school students in Hainan Province, selected by probability proportional sampling and stratified cluster random sampling method. Campus bullying, suicidal tendency and addictive behavior were determined according to the relevant items in the questionnaire on health related behaviors of Chinese students health status and influencing factors questionnaire, and self designed questionnaire. The co occurrence of campus bullying and suicidal tendency among students was analyzed. The binary Logistic regression method was used to analyze the correlation between the co occurrence of campus bullying and suicidal tendency and the addictive behavior of middle school students. Results: The report rate of campus bullying among middle and high school students in Hainan Province was 28.48%, the suicidal tendency was 15.25%, and the co occurrence of campus bullying and suicidal tendency was 8.00%. The results of Logistic regression analysis showed that middle school students and left behind students were prone to campus bullying and suicide tendency ( OR =1.55, 1.52, P <0.05), while Internet addiction, gambling and current smoking showed significant positive correlation with comorbidity of campus bullying and suicide tendency ( OR =3.14, 2.18, 2.07, P < 0.05 ). Conclusions Middle and high school students with addictive behavior have a higher possibility of comorbidity of campus bullying and suicidal tendency. The comprehensive intervention of addictive behavior can reduce the incidence of co occurrence of campus bullying and suicidal tendency, so as to improve health and wellbeing of middle school students.

Objective To investigate the application value of quantitative relaxation parameters based on synthetic MRI technology in the differential diagnosis of parotid gland tumors.Methods Conventional MRI and synthetic MRI data of 59 patients with patho-logically confirmed parotid gland tumors were analyzed retrospectively.T1,T2,and proton density(PD)values of the tumor were extracted from T1,T2 and PD mapping.The differences in quantitative relaxation parameters of pleomorphic adenomas,Warthin tumors,and malignant tumors were further compared.Diagnostic performance of each quantitative relaxation parameter was assessed and com-pared via receiver operating characteristic(ROC)curve and DeLong test.Results T2 value was significantly higher in pleomorphic adenomas than that in malignant tumors(P<0.05).The T1,T2,and PD values of pleomorphic adenomas and malignant tumors were significantly higher than those of Warthin tumors(P<0.05).The area under the curve(AUC)of the T2 value in differentia-ting pleomorphic adenomas from malignant tumors was 0.794.The AUC for T1 value(0.939)in differentiating Warthin tumors from malignant tumors was significantly higher than that of T2(0.873,P=0.341)and PD(0.927,P=0.891)values,without sta-tistically significant difference.The AUC for T2 value(0.968)in differentiating pleomorphic adenomas from Warthin tumors was significantly higher than that of T1(0.931,P=0.360)and PD(0.876,P=0.120)values,without statistically significant difference.Conclusion Quantitative relaxation parameters based on synthetic MRI technology may contribute to differentiating pleomorphic adenomas,Warthin tumors,and malignant tumors of the parotid gland.

Objective:To evaluate the short-term and long-term efficacy of Heidelberg triangle dissection in surgical treatment for pancreatic head cancer.Methods:The clinicopathological data of 97 patients with pancreatic head cancer who underwent pancreaticoduodenectomy at Cangzhou Central Hospital from Jan 2017 to Jan 2020 were retrospectively analyzed. After propensity score matching, 33 patients were included into the Heidelberg group and 36 patients in the control group.Results:There were no significant difference between Heidelberg group and control group in preoperative general conditions and postoperative major complications, while there were more cases with safe surgical margin > 1 mm (81.8% vs. 58.3%, P=0.034) and a significantly higher total number of lymph node dissection (11.24±2.35 vs. 9.50±2.76, P=0.006). In the survival analysis, the cumulative recurrence rate at 12 months (0.182±0.067 vs. 0.444±0.083, P=0.023) and 18 months (0.424±0.086 vs. 0.667±0.079, P=0.024) were better off in the Heidelberg group, and the local recurrence rate in the Heidelberg group was significantly lower than that in the control group (15.3 % vs. 36.1 %, P=0.037). However, there was no statistical difference in the overall survival time between the two groups. Conclusion:Dissection of Heidelberg triangle in radical resection of pancreatic head cancer reduces tumor local recurrence ,while fails to provide survival benefit.

Objective To explore imaging manifestations of crossed ectopic fused kidney.Methods Data of 12 patients with crossed ectopic fused kidney were retrospectively analyzed,and the imaging manifestations of crossed ectopic fused kidney were observed.Results L type crossed ectopic fused kidney was detected in 5 cases,while inferior ectopic type(Ii type),S-shaped type and lump type(O type)ectopic fused kidney was found each in 2 cases,respectively,and doughnut or disc type(C-C type)ectopic fused kidney was noticed in 1 case.The ectopic fused kidney presented with empty one side renal cavity,while the morphology and position of the contralateral kidney were generally normal in all 12 cases,which crossed the midline and fused with the contralateral in situ kidney,including right to left crossed ectopic fusion in 8 cases and left to right crossed ectopic fusion in 4 cases.The ureters of the crossing kidney went across the midline,opened into the bladder trigone on the contralateral side in 11 cases or prostate in 1 case.Combined reproductive system abnormalities were found in 3 cases,including unicornous uterus,bicornuate uterus and cryptorchidism each in 1 case.Two cases were found complicated with abnormal inferior vena cava,including 1 case of both side inferior vena cava and 1 case of left inferior vena cava.Conclusion The imaging manifestations of crossed ectopic fused kidney had characteristics.Complete displaying of reveal fused kidney,ureteral course and opening was helpful to accurate diagnosis and classification of crossed ectopic fused kidney.