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.

BACKGROUND:The implant osseointegration rate of patients with diabetes is low,and the failure rate is high,which seriously affects the quality of life.It is urgent to improve the implant osseointegration of patients with diabetes by effective means to elevate the success rate.Exploring the effect of berberine on the osteogenic differentiation of bone marrow mesenchymal stem cells under a high-glucose environment and its specific mechanism will provide effective theoretical support for solving the above problems. OBJECTIVE:To explore the effect of natural extract berberine on the osteogenic differentiation of rat bone marrow mesenchymal stem cells under the high-glucose microenvironment. METHODS:Bone marrow mesenchymal stem cells of SD rats were cultured by the whole bone marrow adherence method.CCK-8 assay was used to detect the effects of different concentrations of berberine on the proliferation of bone marrow mesenchymal stem cells under the high-glucose environment and to screen out the optimal berberine concentration.The expressions of Runx2 and Osx were detected by alkaline phosphatase activity,alicarin red staining and PCR to determine the effect of berberine on osteogenic differentiation of bone marrow mesymal stem cells under the high-glucose environment.To further explore the underlying mechanism,we introduced the AMPK-specific inhibitor Dorsomorphin and used a DCFH-DA reactive oxygen species fluorescent probe to examine reactive oxygen species levels.The p-AMPK expression was also determined by western blot assay. RESULTS AND CONCLUSION:(1)10 μmol/L was the optimal concentration of berberine to promote bone marrow mesenchymal stem cell proliferation.(2)Alberberine promoted alkaline phosphatase viability of bone marrow mesenchymal stem cells and mineralized nodule formation in a high-glucose microenvironment.(3)Alberberine promoted the expression of Runx2 and OSx in a high-glucose microenvironment.(4)Alberensine effectively inhibited the reactive oxygen species level of bone marrow mesenchymal stem cells in a high-glucose environment.(5)The effects of berberine on promoting bone marrow mesenchymal stem cell osteogenesis and inhibition of reactive oxygen species were reversed by the AMPK inhibitor.(6)Berberine activated AMPK and promoted p-AMPK expression.(7)The above results indicate that berberine(10 μmol/L)promotes the osteogenic differentiation of bone marrow mesenchymal stem cells in a high-glucose environment by activating AMPK and reducing intracellular reactive oxygen species levels.

Objective:To analyze the status of respiratory pathogen detection and the clinical features in children with Mycoplasma pneumoniae pneumonia (MPP). Methods:A prospective, multicenter study was conducted to collect clinical data, including medical history, laboratory examinations and multiplex PCR tests of children diagnosed with MPP from 4 hospitals in China between November 15 th and December 20 th, 2023. The multiplex PCR results and clinical characteristics of MPP children in different regions were analyzed. The children were divided into severe and mild groups according to the severity of the disease. Patients in the severe group were further divided into Mycoplasma pneumoniae (MP) alone and Multi-pathogen co-detection groups based on whether other pathogens were detected besides MP, to analyze the influence of respiratory pathogen co-detection rate on the severity of the disease. Mann-Whitney rank sum test and Chi-square test were used to compare data between independent groups. Results:A total of 298 children, 136 males and 162 females, were enrolled in this study, including 204 children in the severe group with an onset age of 7.0 (6.0, 8.0) years, and 94 children in the mild group with an onset age of 6.5 (4.0, 7.8) years. The level of C-reactive protein, D-dimer, lactic dehydrogenase (LDH) were significantly higher (10.0 (5.0, 18.0) vs. 5.0 (5.0, 7.5) mg/L, 0.6 (0.4, 1.1) vs. 0.5 (0.3, 0.6) mg/L, 337 (286, 431) vs. 314 (271, 393) U/L, Z=2.02, 2.50, 3.05, all P<0.05), and the length of hospitalization was significantly longer in the severe group compared with those in mild group (6.0 (6.0, 7.0) vs. 5.0 (4.0, 6.0) d, Z=4.37, P<0.05). The time from onset to admission in severe MPP children was significantly shorter than that in mild MPP children (6.0 (5.0, 9.5) vs. 9.0 (7.0, 13.0) d, Z=2.23, P=0.026). All patients completed the multiplex PCR test, with 142 cases (47.7%) MPP children detected with 21 pathogens including adenovirus 25 cases (8.4%), human coronavirus 23 cases (7.7%), rhinovirus 21 cases (7.0%), Streptococcus pneumoniae 21 cases (7.0%), influenza A virus 18 cases (6.0%). The pathogens with the highest detection rates in Tianjin, Shanghai, Wenzhou and Chengdu were Staphylococcus aureus at 10.7% (8/75), adenovirus at 13.0% (10/77), adenovirus at 15.3% (9/59), and both rhinovirus and Haemophilus influenzae at 11.5% (10/87) each. The multi-pathogen co-detection rate in severe MPP children was significantly higher than that in mild MPP group (52.9% (108/204) vs. 36.2% (34/94), χ2=10.62, P=0.005). Among severe MPP children, there are 89 cases in the multi-pathogen co-detection group and 73 cases in the simple MPP group. The levels of LDH, D-dimer and neutrophil counts in the multi-pathogen co-detection group were significantly higher than those in the simple MPP group (348 (284, 422) vs. 307 (270, 358) U/L, 0.8 (0.5, 1.5) vs. 0.6 (0.4, 1.0) mg/L, 4.99 (3.66, 6.89)×10 9vs. 4.06 (2.91, 5.65)×10 9/L, Z=5.17, 4.99, 6.11, all P<0.05). Conclusions:The co-detection rate of respiratory pathogens, LDH and D-dimer in children with severe MPP were higher than those with mild MPP. Among severe MPP children the stress response of children in co-detection group was more serious than that of children with simple MPP.

Objective:To analyze the clinical characteristics of patients with spontaneous splenorenal shunt (SSRS) in liver cirrhosis, and to compare the effects and prognosis of different treatments.Methods:The data of cirrhotic patients with SSRS at the First Affiliated Hospital of Zhengzhou University between 2016-2022 were retrospectively analyzed.Patients were divided into Group A receiving conservative treatment, Group B by simple embolization, Group C undergoing TIPS combined with embolization, and Group D given liver transplantation. Life status, liver function changes, incidences of adverse events, and survival between groups were compared.Results:SSRS diameter was positively correlated with blood ammonia ( R=0.478) and negatively correlated with portal vein diameter ( R=-0.301). SSRS diameter is a protective factor for gastrointestinal hemorrhage and ascites and a risk factor for hepatic encephalopathy; Blood ammonia decreased and prothrombin time prolonged after treatment in group A ( P<0.05), blood ammonia decreased and albumin increased in group B ( P<0.05). Hemoglobin and bilirubin increased in group C ( P<0.05), blood ammonia and bilirubin decreased and platelets and albumin increased in group D ( P<0.05); Survival analysis showed that the prognosis of groups A and C was related to liver function, and the survival rate of group D was the highest of all ( P<0.05). Conclusions:SSRS embolization is safe and effective, and liver transplantation improves patient survival. Individualized treatment should be selected based on patient symptoms, liver function, and shunt diameter.

Objective:The preliminary results was reported regarding the treatment of mesenteric torsion by mesenteric fixation in the last decade, especially preventing recurrence of mesenteric torsion by mesenteric fan-shaped fixation.Methods:We selected 12 patients who received emergency operation in Chongqing Hospital of the First Affiliated Hospital of Guangzhou University of Chinese Medicine from December 2010 to March 2022. All of them were made a definite diagnose of mesenteric torsion by the preoperative CT scan or exploratory laparotomy. The recurrence of mesenteric torsion will be prevented by taking the operation of mesenteric fan-shaped fixation. This technique is suitable for the patient who is suffering total mesenteric torsion, but enteric necrosis is excluded affirmatively. The operation is consists of the following progress: (1) Exploratory laparotomy to check for necrosis of the bowel and for lesions other than torsion. (2) Mesenteric torsion derotation.(3) Mesenteric linear fixation; the right posterior lower border of the small mesentery (terminal ileal mesentery) is intermittently sutured to the posterior peritoneum of the right lower quadrant to increase the width of the base of the small mesentery. (4) Mesenteric fan-shaped fixation, which is fan-shaped to the lower left and fixed in the posterior peritoneum, shortening the length of the mesentery and further increasing the width of the mesentery and posterior peritoneal fixation.Results:A total of 12 patients with mesenteric torsion were treated by operation for 15 times in all. Among them, 3 cases received resection of most small bowel were performed without recurrence; 3 patients received only derotation for a total of 4 times, 2 cases recurred, 1 of them recurred twice; 4 cases underwent derotation and mesenteric linear fixation,and 1 case recurred. Four patients with derotation and mesenteric fan-shaped fixation recovered well without recurrence.Conclusion:Mesenteric fan-shaped fixation may be an effective operative type to reduce or avoid postoperative recurrence of mesenteric torsion.

Objective:The preliminary results was reported regarding the treatment of mesenteric torsion by mesenteric fixation in the last decade, especially preventing recurrence of mesenteric torsion by mesenteric fan-shaped fixation.Methods:We selected 12 patients who received emergency operation in Chongqing Hospital of the First Affiliated Hospital of Guangzhou University of Chinese Medicine from December 2010 to March 2022. All of them were made a definite diagnose of mesenteric torsion by the preoperative CT scan or exploratory laparotomy. The recurrence of mesenteric torsion will be prevented by taking the operation of mesenteric fan-shaped fixation. This technique is suitable for the patient who is suffering total mesenteric torsion, but enteric necrosis is excluded affirmatively. The operation is consists of the following progress: (1) Exploratory laparotomy to check for necrosis of the bowel and for lesions other than torsion. (2) Mesenteric torsion derotation.(3) Mesenteric linear fixation; the right posterior lower border of the small mesentery (terminal ileal mesentery) is intermittently sutured to the posterior peritoneum of the right lower quadrant to increase the width of the base of the small mesentery. (4) Mesenteric fan-shaped fixation, which is fan-shaped to the lower left and fixed in the posterior peritoneum, shortening the length of the mesentery and further increasing the width of the mesentery and posterior peritoneal fixation.Results:A total of 12 patients with mesenteric torsion were treated by operation for 15 times in all. Among them, 3 cases received resection of most small bowel were performed without recurrence; 3 patients received only derotation for a total of 4 times, 2 cases recurred, 1 of them recurred twice; 4 cases underwent derotation and mesenteric linear fixation,and 1 case recurred. Four patients with derotation and mesenteric fan-shaped fixation recovered well without recurrence.Conclusion:Mesenteric fan-shaped fixation may be an effective operative type to reduce or avoid postoperative recurrence of mesenteric torsion.

Purpose/Significance To classify the elderly according to their heterogeneous health status,and to explore the potential categories and influencing factors status,so as to promote the precision of health information services for the elderly.Method/Process Based on the data of the China health and retirement longitudinal study(CHARLS)database in 2018,the elderly are classified according to their health status by the method of latent class analysis,and the main influencing factors are identified by regression analysis.Result/Conclusion The elderly could be divided into 4 categories according to their health status.Age,sex,education level and retirement sta-tus are significant factors affecting the health grouping of the elderly.According to the heterogeneous health characteristics of the elderly,the service optimization strategy should be provided to promote the physical and mental health of the elderly.

Vibrio parahaemolyticus is a major pathogen frequently found in seafood. Rapid and accurate detection of this pathogen is important for the control of bacterial foodborne diseases and to ensure food safety. In this study, we established a one-pot system that combines uracil-DNA glycosylase (UDG), loop-mediated isothermal amplification (LAMP), and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 12b (Cas12b) for detecting V. parahaemolyticus in seafood. This detection system can effectively perform identification using a single tube and avoid the risk of carry-over contamination.
Vibrio parahaemolyticus/genetics* ; Uracil-DNA Glycosidase/genetics* ; Hot Temperature ; CRISPR-Cas Systems ; Food Safety

Objective:To explore the correlation between blood glucose level and parental education level in children with type 1 diabetes mellitus (T1DM) based on mobile health APP.Methods:The data of T1DM children enrolled in China′s T1DM registration management program and registered to use TangTangquan ? were collected, as well as the blood glucose monitoring information uploaded quarterly after registration. Children were divided into low education group (middle school or below) and high education group (junior college or above) according to their parents′ education level. Blood glucose levels were compared between the two groups at different time points. Spearman correlation analysis and multivariate logistic regression analysis were used to evaluate the correlation between blood glucose level and parents′ education level in children with T1DM. Results:A total of 2 263 eligible children with T1DM were included and 1 246 were female (55.1%). The median age was 7.9(4.4, 11.4)years and T1DM duration was 0.07(0.02, 0.46)years. Among them, 1 513 cases were in the low-education group while 750 cases were in the high-education group. Within three years after registration, the glucose levels of each interval in the low-education group were increasing gradually (all P<0.05 except post-breakfast glucose). The glucose levels of each interval in the high-education group in the third year were lower than those in the low-education group (all P<0.05 except nocturnal glucose). The result of multivariate logistic regression analysis showed that after the adjustment of factors including T1DM duration and treatment, parental educational levels were still the separate related factors of premeal glucose, bedtime glucose and nocturnal glucose (premeal glucose: OR=0.385, 95% CI: 0.164-0.874, P=0.025; bedtime glucose: OR=0.444, 95% CI: 0.204-0.949, P=0.038; nocturnal glucose: OR=0.226, 95% CI: 0.582-0.747, P=0.020). Conclusions:The blood glucose levels of children with T1DM were negatively associated with parental educational levels. It is suggested that parental educational levels should be taken into consideration in the management of T1DM for children.

Objective:To investigate the effect of cumulative serum uric acid (cumSUA) on early-onset ischemic stroke in young adults.Methods:A prospective cohort study was conducted. A total of 15 607 Kailuan workers who participated in at least two physical check-ups in 2006 and 2008 and at the time of the last physical check-up before 2014 were selected as subjects. Cumulative uric acid exposure during the follow-up period was calculated. The subjects were divided into three groups according to the quantile of cumSUA: the first quantile group was cumSUA<1 563 μmol/L·year, the second quantile group was: 1 563 μmol/L·year≤cumSUA<1 996 μmol/L·year, the third group was cumSUA≥1 996 μmol/L·year. The time of the last physical check-up was regarded as the starting point of follow-up, and early-onset ischemic stroke was regarded as the end event. Kaplan-Meier was used to calculate the incidence of early-onset ischemic stroke in different groups, and Log-rank method was used to calculate the differences in the incidence of early-onset ischemic stroke among different groups. Multivariate Cox regression model was used to analyze the risk of early-onset ischemic stroke in different groups. A four-node (5th, 25th, 75th, 95th percentile) restricted cubic spline plot was used to assess the dose-response relationship between cumSUA and early-onset ischemic stroke.Results:A total of 15 607 subjects were followed up for (7.3±1.1) years. 100 cases with early-onset ischemic stroke were observed with an average age of (46±4) years old. The number of events in the first, second, and third quartile groups was 18, 35, and 47, respectively, and the cumulative incidence rates in the first, second, and third quartile groups were 0.40%, 0.77%, and 1.07%, respectively. The difference in cumulative incidence of endpoint events between the groups was statistically significant by Log-rank test ( χ2=14.96, P=0.003). The results of Cox regression analysis showed that after correcting for confounders, the HR(95% CI) for early-onset ischemic stroke in the second and third quartile groups was [1.67(0.92,3.00), P=0.090; 2.05(1.48,3.69), P=0.020]. Restricted cubic spline results showed a nonlinear correlation between cumSUA and early-onset ischemic stroke after adjysted for confounders. Conclusion:Cumulative serum uric acid is positively correlated with the risk of early-onset ischemic stroke in young adults.