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 precise classify sacral meningeal cysts, effective guide minimally invasive neurosurgery and postoperative personalized rehabilitation by multiple dimensions radiographic reconstruction MRI. METHODS: From March to December 2021, based on the original 3D-fast imaging employing steadystate acquisition (FIESTA) scanning sequence, 92 patients with sacral meningeal cysts were pre-operatively evaluated by multiple dimensional reconstruction MRI. The shape of nerve root and the leakage of cyst were reconstructed according to the direction of nerve root or leakage track showed on original MRI scans. Sacral canal cysts were accurately classified as including nerve root and without nerve root, so as to accurately design the incision of skin and formulate corresponding open range of the posterior wall of the sacral canal. Under the microscope intraoperation, the shape of the nerve roots inside cysts or leakage track of the cysts without nerve roots were verified and explored. After the reinforcement and shaping operation, several reexaminations of multiple dimensional reconstruction MRI were performed to understand the deformation of the nerve root and hydrops in the operation cavity, so as to formulate a persona-lized rehabilitation plan for the patients. RESULTS: Among the 92 patients with sacral mengingeal cyst, 58 (63.0%) cysts with nerve root cyst, 29 (31.5%) cysts without nerve root cyst, and 5 (5.4%) cysts with mixed sacral canal cyst. In 58 patients with nerve root cysts, the accuracy of preoperative clinical classification on MRI image reached 96.6% (56/58) through confirmation by operating microscope. Only 2 cases of large single cyst with nerve root on the head of cyst were mistaken for without nerve root type. In 29 patients with sacral cyst without nerve root, the accuracy of preoperative image reached 100% through confirmation by operating microscope. The accuracy of judging the internal nerve root and leakage of 12 cases with recurrent sacral cyst was also 100%. Two cases of delayed postoperative hydrops were found one month after operation. After rehabilitation treatment by moxibustion and bathing, the hydrops disappeared 4-6 months after operation. CONCLUSION Multiple dimensional reconstruction MRI can precisely make clinical classification of sacral meningeal cysts before operation, guide minimally invasive neurosurgery effectively, and improve the rehabilitation effect.
Humans ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Sacrum/surgery* ; Adult ; Middle Aged ; Imaging, Three-Dimensional/methods* ; Cysts/rehabilitation* ; Aged ; Adolescent ; Young Adult ; Spinal Nerve Roots/diagnostic imaging* ; Minimally Invasive Surgical Procedures ; Neurosurgical Procedures/methods*

OBJECTIVE: To investigate whether Buyang Huanwu Decoction (BYHWD) had a good curative effect on the neuroprotection of red nucleus neurons after spinal cord injury (SCI) and the possible molecular mechanism. METHODS: Ninety male Sprague-Dawley rats were divided into 5 groups (n=18 per group) according to a random number table, including the control, model, low- (12.78 g/kg, BL group), medium- (25.65 g/kg, BM group), and high-dose BYHWD groups (51.30 g/kg, BH group). A rubrospinal tract transection model in rats was established, and different doses of BYHWD were intragastrically administrated for 4 weeks. The forelimb locomotor function was recorded using the spontaneous vertical exploration test. Cyclic adenosine monophosphate (cAMP) level in red nucleus was detected through an enzyme-linked immunosorbent assay. The morphology and number of red nucleus neurons were observed using Nissl's staining and axonal retrograde tracing by Fluoro-Gold (FG). The expression of cAMP-dependent protein kinase A (PKA), nuclear factor kappa-B (NF-κB) p65, and brain-derived neurotrophic factor (BDNF) in red nucleus were detected using immunohistochemistry and quantitative real-time polymerase chain reaction. RESULTS: Compared with the control group, the utilization rate of bilateral forelimbs, unilateral right forelimbs, proportion of FG-labeled positive neurons, cAMP level, protein expressions of PKA and BDNF, and BDNF mRNA expression were significantly decreased in the model group (P<0.01), while NF-κB p65 was increased in the model group (P<0.01). Compared with the model group, the utilization rate of bilateral forelimbs and unilateral right forelimbs were significantly higher in the BL, BM and BH groups (P<0.01), the proportion of FG-labeled positive neurons, cAMP level, protein expressions of PKA and BDNF and BDNF mRNA expression in all BYHWD groups were increased (P<0.05 or P<0.01), while NF-κB p65 were decreased in all BYHWD groups (P<0.05 or P<0.01). CONCLUSIONS BYHWD possesses a sound neuroprotective effect on red nucleus neurons after SCI, and the efficacy was dose-related. The mechanism may be related to regulating the cAMP/PKA/NF-κ B p65 signaling pathway, finally promoting expression of BDNF.
Animals ; Spinal Cord Injuries/pathology* ; Drugs, Chinese Herbal/therapeutic use* ; Rats, Sprague-Dawley ; Male ; Cyclic AMP/metabolism* ; Transcription Factor RelA/metabolism* ; Cyclic AMP-Dependent Protein Kinases/metabolism* ; Signal Transduction/drug effects* ; Brain-Derived Neurotrophic Factor/genetics* ; Red Nucleus/metabolism* ; Recovery of Function/drug effects* ; Neurons/metabolism* ; Rats

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective:Taking Inflammatory Bowel Disease(IBD)patients as an example,to explore the impact of disparities in regional outpatient security policies on medication reimbursement benefits for patients,and to provide insights for promoting the reform and development of equal outpatient security policy.Methods:39 cities from 9 provinces in China were selected as research samples to analyze the types,coverage,and benefits of their outpatient security policies.Indicators such as the individual out-of-pocket ratio,deductible,and specified reimbursement rate were used to simulate the actual reimbursement ratio for IBD patients using negotiated drugs.Results:Under the general outpatient coordination policy,the average actual reimbursement rate for medications in IBD patients was 26.36%for residents and 36.47%for employees.Under the outpatient chronic and special disease policy,the average actual reimbursement rate was 42.49%for residents and 50.94%for employees,while patients receiving drug treatment under the outpatient special drug policy have an average actual reimbursement rate of 51.62%(for residents)and 64.92%(for employees).Conclusion:Under China's outpatient security policies,there are significant disparities in reimbursement benefits for IBD patients across different regions.Therefore,it is recommended to strengthen the coordination of outpatient security policies across regions,optimize policy design,and provide patients with more equitable and accessible medical coverage.

In view of the characteristics of H5N6 subtype avian influenza virus(AIV)that it has both high pathogenicity and the risk of cross-species transmission,posing a serious threat to the poultry farming industry and public health security,in order to effectively prevent and control the spread of H5N6 avian influenza,a rapid,sensitive and specific detection technolo-gy was established in this study.The specific monoclonal antibodies against the neuraminidase N6 protein of avian influenza A virus subtype H5N6 were obtained through hybridoma and monoclonal antibody technology.These antibodies were coupled and labeled with carboxyl-functionalized fluorescent quantum dots,along with previously prepared specific antibodies against the hemagglutinin H5 protein.A rapid fluorescence immunochromatographic detection method for the H5N6 subtype of avian influ-enza virus was established according to the principle of double-antibody sandwich immunochromatography.This method a-chieved a detection sensitivity of 1 ng/mL for recombinant hemagglutinin H5 subtype protein and 0.1 ng/mL for recombinant neuraminidase N6 subtype protein.Moreover,the method exhibited no cross-reactivity with other influenza subtypes or patho-gens,such as Newcastle disease(ND),infectious bronchitis(IB),and infectious laryngotracheitis(ILT),thus demonstrating good specificity.The method effectively identified the highly pathogenic avian influenza virus H5 subtype and directly distin-guished the H5N6 subtype with good accuracy.The fluorescent quantum dot immunochromatographic typing detection method established herein met the sensitivity,specificity,and accuracy requirements for H5N6 subtype detection,and can be further used for rapid detection of the H5 and H5N6 subtypes of avian influenza virus.

In a healthy human, the airway mucus forms a thin, protective liquid layer covering the surface of the respiratory tract. It comprises a complex blend of mucin, multiple antibacterial proteins, metabolic substances, water, and electrolytes. This mucus plays a pivotal role in the lungs' innate immune system by maintaining airway hydration and capturing airborne particles and pathogens. However, heightened mucus secretion in the airway can compromise ciliary clearance, obstruct the respiratory tract, and increase the risk of pathogen colonization and recurrent infections. Consequently, a thorough exploration of the mechanisms driving excessive airway mucus secretion is crucial for establishing a theoretical foundation for the eventual development of targeted drugs designed to reduce mucus production. Across a range of lung diseases, excessive airway mucus secretion manifests with unique characteristics and regulatory mechanisms, all intricately linked to mucin. This article provides a comprehensive overview of the characteristics and regulatory mechanisms associated with excessive airway mucus secretion in several prevalent lung diseases.
Humans ; Mucus/metabolism* ; Mucins/physiology* ; Lung Diseases/metabolism* ; Respiratory Mucosa/metabolism* ; Pulmonary Disease, Chronic Obstructive/physiopathology* ; Asthma/physiopathology* ; Cystic Fibrosis/physiopathology* ; Mucociliary Clearance/physiology*

Qualitative and quantitative analysis methods for chemical components of different processed products of Corni Fructus were established to systematically characterize and identify these components, and the content of the main differential components was determined. The chemical components of different processed products of Corni Fructus were collected using ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS). Through analysis of self-built databases, literature, and reference standards, a total of 93 components were obtained, including 19 iridoids, 15 flavonoids, 16 organic acids, eight triterpenoids, eight tannins, four amino acids, two polysaccharides, five olefins, and 16 other compounds. Additionally, by using multivariate statistical methods, the differential components between different processed products of Corni Fructus were screened under the conditions of VIP>1.0 and FC<0.5 or FC>2.0 and P<0.05. The PCA and OPLS-DA results showed differences in the chemical components between different processed products of Corni Fructus. A total of 21 differential components were screened, including tartaric acid, morroniside, and rutin. On this basis, ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS/MS) was used to determine the content of 10 main common differential components, including gallic acid, morroniside, ursolic acid, loganin, swertiamarin, rutin, 5-hydroxymethylfurfural, cornuside Ⅰ, quercetin, and oleanolic acid. The above 10 components showed a good linear relationship within the determined concentration range, with the precision, stability, repeatability, and sample recovery rate all meeting the requirements. Compared with that in Corni Fructus, the content of iridoid glycosides in wine-prepared Corni Fructus and wine-and honey-prepared Corni Fructus decreased, while the content of gallic acid, rutin, quercetin, 5-hydroxymethylfurfural, ursolic acid, and oleanolic acid increased. Compared with wine-prepared Corni Fructus, wine-and honey-prepared Corni Fructus showed varying degrees of increase in all other components, except for a slight decrease in gallic acid content. In summary, this study clarified the influence of different processing methods on the chemical components of Corni Fructus, providing a theoretical basis for the scientific connotation, overall quality evaluation, and clinically rational application of Corni Fructus processing in the future.
Tandem Mass Spectrometry/methods* ; Chromatography, High Pressure Liquid/methods* ; Cornus/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Fruit/chemistry*

As a new type of production factor that can empower the development of new quality productivity, the data element is an important engine to promote the high quality development of the industry. Traditional Chinese medicine(TCM) dispensing is the most basic work of TCM clinical pharmacy, and its quality directly affects the clinical efficacy of TCM. The integration of data elements and TCM dispensing can stimulate the innovation and vitality of the TCM dispensing industry and promote the high-quality and sustainable development of the industry. A large-scale, detailed, and systematic study on TCM dispensing was conducted. The innovative practice path of data fusion construction in the whole process of TCM dispensing was investigated by integrating the digital resources "nine full activities" of TCM dispensing, creating the digital dictionary of "TCM clinical information data elements", and exploring innovative applications of TCM dispensing driven by data and technology, so as to promote the standardized, digital, and intelligent development of TCM dispensing in medical health services. The research content of this project was successfully selected as the second batch of "Data element×" typical cases of National Data Administration in 2024, which is the only selected case in the field of TCM.
Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal ; Humans