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 explore the efficacy, adverse reactions, and feasibility of high-definition transcranial direct current stimulation(HD-tDCS) treating major depressive disorder(MDD) patients with anxious distress.Methods:Sixty cases of MDD with anxious distress admitted to Zhenjiang Mental Health Center were recruited as participants. All patients were allocated into either the active treatment group or the sham group based on the random number table method. HD-tDCS was utilized in both groups to stimulate the left dorsolateral prefrontal cortex on the basis of conventional antidepressant treatment. In the active group, 2mA current stimulation was used for 20 min, and in the sham group, a 30-sceond stimulation was adopted at the beginning and the end of the stimulation. Participants in both group were treated once a day, five times a week for two consecutive weeks. Anxiety and depression symptoms of the patients were assessed respectively by the Hamilton depression scale(HAMD 17), the Montgomery-Asberg Depression Rating Scale(MARDS), the Hamilton Anxiety Scale(HAMA), and the Beck Anxiety Inventory(BAI) at the baseline, 2nd, 4th, and the 6th weekend of the treatment. The differences between active treatment and sham groups were analyzed by repetitive measure analysis of variance and simple effect analysis. Fisher′s exact probability test was used to compare the effective rate, remission rate and adverse reaction rate between the two groups. Results:(1) The interaction of times and groups was significant in HAMD 17( F=3.29, P<0.05) and BAI( F=2.99, P<0.05). In all measurement instruments, the main effects of groups( F=4.40-7.94) and times( F=35.42-247.59) were significant( P<0.05).(2) Findings from the simple effect analysis showed that: there were no significant differences in the scores of HAMD 17 at baseline and the 2 nd assessment between the two groups. Similarly, no significant differences were found in BAI at baseline, the 2nd and the 6th weekend of the treatment between two groups( P>0.05).(3) The scores of HAMD 17 at the 4th and the 6th week, BAI at the 4th weekend of the treatment in the active group were significantly lower than that in the sham group( P<0.05).(4) At the 4th weekend of the treatment, the active group had a remission rate of 16/20 and a response rates of 19/20, which were higher than 9/19 and 13/19, respectively, in the sham group( P<0.05). Also, the remission rate(18/20) in the active group was higher than that in the sham group(11/19) at the 6th weekend of the treatment.( P<0.05). As for the response rates, differences were not found between the two groups at the 6th weekend of the treatment.(5) The overall dropout rate had no significant differences in-between( P>0.05). As for the safety outcome, the rate of adverse events(e.g., itching, tingling and headache) showed no significant differences between the two groups. Additionally, no severe adverse events or mania was reported. Conclusions:This study indicated that HD-tDCS has significant efficacy and high safety in the treatment among MDD patient with anxious distress. Nevertheless, further large sample clinical studies are warranted to confirm the findings of the current investigation.

Objective:To explore the efficacy, adverse reactions, and feasibility of high-definition transcranial direct current stimulation(HD-tDCS) treating major depressive disorder(MDD) patients with anxious distress.Methods:Sixty cases of MDD with anxious distress admitted to Zhenjiang Mental Health Center were recruited as participants. All patients were allocated into either the active treatment group or the sham group based on the random number table method. HD-tDCS was utilized in both groups to stimulate the left dorsolateral prefrontal cortex on the basis of conventional antidepressant treatment. In the active group, 2mA current stimulation was used for 20 min, and in the sham group, a 30-sceond stimulation was adopted at the beginning and the end of the stimulation. Participants in both group were treated once a day, five times a week for two consecutive weeks. Anxiety and depression symptoms of the patients were assessed respectively by the Hamilton depression scale(HAMD 17), the Montgomery-Asberg Depression Rating Scale(MARDS), the Hamilton Anxiety Scale(HAMA), and the Beck Anxiety Inventory(BAI) at the baseline, 2nd, 4th, and the 6th weekend of the treatment. The differences between active treatment and sham groups were analyzed by repetitive measure analysis of variance and simple effect analysis. Fisher′s exact probability test was used to compare the effective rate, remission rate and adverse reaction rate between the two groups. Results:(1) The interaction of times and groups was significant in HAMD 17( F=3.29, P<0.05) and BAI( F=2.99, P<0.05). In all measurement instruments, the main effects of groups( F=4.40-7.94) and times( F=35.42-247.59) were significant( P<0.05).(2) Findings from the simple effect analysis showed that: there were no significant differences in the scores of HAMD 17 at baseline and the 2 nd assessment between the two groups. Similarly, no significant differences were found in BAI at baseline, the 2nd and the 6th weekend of the treatment between two groups( P>0.05).(3) The scores of HAMD 17 at the 4th and the 6th week, BAI at the 4th weekend of the treatment in the active group were significantly lower than that in the sham group( P<0.05).(4) At the 4th weekend of the treatment, the active group had a remission rate of 16/20 and a response rates of 19/20, which were higher than 9/19 and 13/19, respectively, in the sham group( P<0.05). Also, the remission rate(18/20) in the active group was higher than that in the sham group(11/19) at the 6th weekend of the treatment.( P<0.05). As for the response rates, differences were not found between the two groups at the 6th weekend of the treatment.(5) The overall dropout rate had no significant differences in-between( P>0.05). As for the safety outcome, the rate of adverse events(e.g., itching, tingling and headache) showed no significant differences between the two groups. Additionally, no severe adverse events or mania was reported. Conclusions:This study indicated that HD-tDCS has significant efficacy and high safety in the treatment among MDD patient with anxious distress. Nevertheless, further large sample clinical studies are warranted to confirm the findings of the current investigation.

Objective To investigate the application of 3-D scanning in the diagnosis and evaluation of pectus excava-tum.Methods From July 2016 to June 2017, chest CT concomitant 3-D scanning were performed in 90 pectus excavatum pa-tients before Nuss procudure.Another 30 cases underwent chest CT scanning for non-chest deformity causes were chosen as a control group.The transverse and anterior-posterior maximum diameter through the deepest point of chest wall deformity were measured.The surface topography index and Haller index were calculated respectively .Results There was a positive correla-tion between CT and 3-D scanning diameters of the transverse and anterior-posterior maximum diameters, and consistency rates were 94% and 82%, respectively.There was significant difference between pectus excavatum group 1.82 ±0.21 and control group 1.41 ±0.07 in the STI(P<0.001).There was a positive correlation between Haller index 5.12 ±3.36 and STI 1.82 ± 0.21, and consistency rate was 89%.The Delong's test showed no significant difference between ROC of HI and STI(Z =1.18, P=0.28).Conclusion 3-D scanning and STI of pectus excavatum is a validated alternative for CT and Haller index, especially in the infant and non-surgical treatment PE cases.

Spinal cord stimulation (SCS) is a promising technique for treating disorders of consciousness (DOCs). However, differences in the spatio-temporal responsiveness of the brain under varied SCS parameters remain unclear. In this pilot study, functional near-infrared spectroscopy was used to measure the hemodynamic responses of 10 DOC patients to different SCS frequencies (5 Hz, 10 Hz, 50 Hz, 70 Hz, and 100 Hz). In the prefrontal cortex, a key area in consciousness circuits, we found significantly increased hemodynamic responses at 70 Hz and 100 Hz, and significantly different hemodynamic responses between 50 Hz and 70 Hz/100 Hz. In addition, the functional connectivity between prefrontal and occipital areas was significantly improved with SCS at 70 Hz. These results demonstrated that SCS modulates the hemodynamic responses and long-range connectivity in a frequency-specific manner (with 70 Hz apparently better), perhaps by improving the cerebral blood volume and information transmission through the reticular formation-thalamus-cortex pathway.
Adolescent ; Adult ; Brain ; physiopathology ; Consciousness ; physiology ; Consciousness Disorders ; physiopathology ; therapy ; Female ; Hemodynamics ; physiology ; Humans ; Male ; Middle Aged ; Pilot Projects ; Spinal Cord ; physiopathology ; surgery ; Spinal Cord Stimulation ; methods ; Young Adult