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 available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective To explore the mechanism of Tongyangxiao Lotion(TYX)for promoting wound healing following surgery for anal fistula.Methods The active ingredients and drug targets of TYX were explored using TCMSP and BATMAN databases,and the targets associated with wound healing were screened using GeneCards and OMIM databases;the intersecting drug and wound-related targets were analyzed with protein-protein interaction(PPI)analysis and GO and KEGG enrichment analyses.In 25 SD rat models with simulated anal fistula surgery,the effect of wound dressing with TYX at low,medium and high doses(once daily for 14 days)on wound healing were assessed in comparison with potassium permanganate(PP)solution.The granulation tissues collected from the wounds were examined for pathological changes with HE staining and for TNF-α expression using immunohistochemistry.The expressions of 1β,TNF-α,IL-6 mRNA and proteins in the granulation tissue were detected using RT-qPCR,Western blotting or ELISA.Results Network pharmacology analysis yielded 156 common targets between TYX and wound healing,and among them IL-1β,TNF-α,and IL-6 were identified as potential targets of TYX for promoting wound healing.Six core components of TYX were capable of binding to IL-1β,TNF-α,and IL-6 with binding energies all below-6.0 Kcal/mol.In the rat models,the wounds with TYX and PP solution dressing showed significantly reduced inflammatory cell infiltration and increased fibroblasts and collagen deposition.TYX at the 3 doses and PP solution all significantly reduced the expressions of IL-6,IL-1β,TNF-α mRNA and IL-6 protein in the granulation tissues,but TYX at the medium and high doses produced significantly stronger effects than PP solution for lowering TNF-α protein expression and mRNA expressions of TNF-α and IL-6.Conclusion TYX accelerates wound healing by down-regulating the inflammatory factors and reducing inflammation in the wounds.

Objective To explore the mechanism of Tongyangxiao Lotion(TYX)for promoting wound healing following surgery for anal fistula.Methods The active ingredients and drug targets of TYX were explored using TCMSP and BATMAN databases,and the targets associated with wound healing were screened using GeneCards and OMIM databases;the intersecting drug and wound-related targets were analyzed with protein-protein interaction(PPI)analysis and GO and KEGG enrichment analyses.In 25 SD rat models with simulated anal fistula surgery,the effect of wound dressing with TYX at low,medium and high doses(once daily for 14 days)on wound healing were assessed in comparison with potassium permanganate(PP)solution.The granulation tissues collected from the wounds were examined for pathological changes with HE staining and for TNF-α expression using immunohistochemistry.The expressions of 1β,TNF-α,IL-6 mRNA and proteins in the granulation tissue were detected using RT-qPCR,Western blotting or ELISA.Results Network pharmacology analysis yielded 156 common targets between TYX and wound healing,and among them IL-1β,TNF-α,and IL-6 were identified as potential targets of TYX for promoting wound healing.Six core components of TYX were capable of binding to IL-1β,TNF-α,and IL-6 with binding energies all below-6.0 Kcal/mol.In the rat models,the wounds with TYX and PP solution dressing showed significantly reduced inflammatory cell infiltration and increased fibroblasts and collagen deposition.TYX at the 3 doses and PP solution all significantly reduced the expressions of IL-6,IL-1β,TNF-α mRNA and IL-6 protein in the granulation tissues,but TYX at the medium and high doses produced significantly stronger effects than PP solution for lowering TNF-α protein expression and mRNA expressions of TNF-α and IL-6.Conclusion TYX accelerates wound healing by down-regulating the inflammatory factors and reducing inflammation in the wounds.

Objective To explore potential genes associated with the pathogenesis of hypospadias using weighted Gene co-expression network analysis(WGCNA).Methods The WGCNA algorithm was used to process the hypospadias-related dataset GSE35034,and then a gene co-expression weight network was constructed to screen the modules with the highest correlation with hypospadias,and the genes in the modules were enriched and detected by gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG).Differential analysis was also performed to screen out differential genes.The differential genes were imported into the String database.Using Cytoscape software,the hub genes in the network were identified.The results screened by the above three methods were combined and analyzed,and the core genes in the intersection set were screened.Using the external dataset GSE121712,the core genes were verified by mRNA expression changes and subject work characterization receiver operating characteristic(ROC)curve diagnosis.Results Fifteen co-expression modules were obtained based on the WGCNA method.Ninety-three common differential genes meeting the conditions were obtained by differential analysis.Ten core genes were finally obtained by Cytoscape software analysis.Finally MEbrown module,differential genes and the 10 core genes yielded a total of 2 intersecting genes:FBXL16 and SYNDIG1.ROC curves verified that the intersecting genes were differentially expressed in patients with hypospadias versus normal subjects.Conclusion In this study,two key genes with significant correlation with hypospadias were obtained by WGCNA,which may be used for the early diagnosis and treatment of hypospadias after further study.

Tumor-associated macrophages (TAMs) are the main immune cells in the tumor microenvironment, mainly divided into M1 type macrophages which are pro-inflammatory and anti-tumor and M2 type macrophages that are anti-inflammatory and can promote the growth of tumor. M2 macrophages play a crucial role in the occurrence, development and metastasis of tumor, are often closely related to poor prognosis, and have become an important target of tumor immunotherapy. Nanomedicine can achieve specific targeting of TAMs and improve drug safety. Therefore, the use of nanomedicine to regulate TAMs has broad application prospects. Using nanoparticles to deplete TAMs, inhibit their recruitment or reprogram M2 macrophages into M1 macrophages, or using TAMs to deliver nanomedicine has shown great potential for clinical application. In this paper, the role of TAMs-based nanomedicine in tumor immunotherapy was elaborated, and the existing problems and suggestions were discussed.

Objective:To investigate the diagnostic efficiency of the 2020 Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) and the 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS) in the diagnosis of benign and malignant thyroid nodules.Methods:A retrospective analysis of the two-dimensional ultrasound image results of 324 thyroid nodules in 289 patients with thyroid nodules and thyroid nodules were performed in the physical examination of the Health Management Department of the Guangdong Second Provincial General Hospital from January 2018 to January 2019. A superficial professional doctor with a senior professional title simultaneously uses the C-TIRADS and ACR-TIRADS methods to evaluate the above nodules. The results are all pathologically referenced for the χ2 test and the receiver operating characteristic curve is drawn. Results:The sensitivity of C-TIRADS in diagnosing benign and malignant thyroid nodules was 81.90%, specificity was 97.72%, accuracy was 92.59%, negative predictive value was 91.85%, positive predictive value was 84.51%; ACR-TIRADS diagnosis The sensitivity of benign and malignant thyroid nodules was 59.05%, specificity was 99.54%, accuracy was 86.42%, negative predictive value was 83.52%, and positive predictive value was 98.41%. The area under the ROC curve was 0.958 and 0.935( Z=2.31 P=0.021). Conclusion:C-TIRADS classification based on counting method is better than ACR-TIRADS classification based on sub-method in the diagnosis of thyroid nodules. It has better efficacy and is more suitable for the current status of diagnosis and treatment of thyroid nodules in China.

OBJECTIVE： To establish the method for the rapidly non-destructive quality control of Liuwei dihuang capsule. METHODS： AOTF-NIR spectrometry was adopted. Taking 80 batches of Liuwei dihuang capsule produced by a manufacturer in recent three years as samples， HPLC chromatogram was adopted to determine the contents of loganin， morroniside， paeonol， paeoniflorin and ursolic acid； the content of water was determined according to general principles stated in 2015 edition of Chinese Pharmacopeia （part Ⅰ）. Taking 70 batches of samples as correction set， the partial least square method and the cross-validation algorithm were used to establish the NIR quantitative model of 6 indexes in Liuwei dihuang capsules with the Unscrambler quantitative analysis software. Taking residual 10 batches of samples as validation set， external validation was conducted for the model. RESULTS： The correlation coefficients （R2） of internal and external validation of loganin， morroniside， paeonol， paeoniflorin， the content of water quantitative model were all greater than 0.9； the correction of standand deviation （RMSEC） were 0.372 8， 0.025 4， 0.263 3， 0.288 5， 0.186 7 and 0.037 7； the prediction of standard deviation （RMSEP） were 0.462 2， 0.077 5， 0.472 1， 0.634 9， 0.293 4 and 0.206 9； the external verification showed that mean deviations of preclicted value to actual value were 6.04％， 6.05％， 5.87％， 6.97％， 5.62％ and 4.83％， with the mean deviation less than 10％.CONCLUSIONS：The established method can achieve rapidly non-destructive analysis Liuwei dihuang capsule.

OBJECTIVE： To study the chemical constituents from the petroleum ether part from whole herbs of Pteris vittata. METHODS： The petroleum ether part from whole herbs of P. vittata was separated and isolated by silica gel column， gel column， recrystallization and TLC. The structures of the compounds were identified according to physicochemical properties and spectrum data （1H-NMR and 13C-NMR）. RESULTS： A total of 11 compounds were isolated and identified from the petroleum ether part from whole herbs of P. vittata， as （2R）-acetyl pterosin B （Ⅰ）， palmitic acid （Ⅱ）， hop-22（29）-ene （Ⅲ）， epifriedelanol （Ⅳ）， lupenone （Ⅴ）， olean-18-en-3-one （Ⅵ）， stigmasterol （Ⅶ）， β-sitosterol （Ⅷ）， 22-hydroxyhopane （Ⅸ）， ergosterol （Ⅹ）， β-sitosterol acetate （Ⅺ）. CONCLUSIONS： Compounds Ⅰ-Ⅶ and Ⅸ-Ⅺ are isolated from this plant for the first time， and can provide theoretic reference for further studying bioactive pharmacodynamic substances in P. vittata and enriching chemical component data.

OBJECTIVE:To establish the method for rapid quality evaluation of Astragali Radix.METHODS:The moisture of medicinal material was determined by oven drying method;the content of astragaloside Ⅳ was determined by HPLC-ELSD;the content of isoflavone glucoside was determined by HPLC (as reference value).The partial least squares (PLS) method combined with acousto-optic turnable filter-NIDRS was adopted to build quantitative model of above indexes in Astragali Radix (as predict value).According to reference value,60 batches of sample were collected.The spectra pretreatment was conducted by first derivative method combined with Savitzky golay.The optimal bands of moisture,astragaloside Ⅳ and isoflavone glucoside were 1 100-2 300 nm,1 080-2 160 nm,1 170-2 230 nm,respectively.RESULTS:The content determination of moisture,astragaloside Ⅳ and isoflavone glucoside in samples were all in line with methodology requirements.The corrected mean square root deviation of quantitative model for moisture,astragaloside Ⅳ,calycosin glucoside were 0.132 3,0.006 6,0.002 5,respectively;predicted mean square root deviation were 0.237 1,0.016 3,0.004 7;internal cross validation coefficient of correction set were 0.975 9,0.953 3,0.968 0;internal verification deviation of quantitative model were 1.43％,1.90％,1.84％;external verification deviation were 1.73 ％,2.68 ％,2.71％,respectively.CONCLUSIONS:The method is rapid,accurate,simple,pollution-free,and can be used for rapid quality evaluation of Astragali Radix.