BACKGROUND:Successful uterine spiral artery remodeling is necessary for normal pregnancy,in which vascular smooth muscle cells are important cells.Interferon-γ is associated with the loss of vascular smooth muscle cells during early pregnancy.However,the specific mechanism is not fully understood. OBJECTIVE:To investigate the effects of interferon-γ on migration and apoptosis of vascular smooth muscle cells through NLRP3/caspase-1/GSDMD pyroptosis pathway. METHODS:Human vascular smooth muscle cells were divided into control group and interferon-γ group.The control group was cultured normally,and the interferon-γ group was treated with 10 ng/mL interferon-γ for 24 hours.The migration ability of vascular smooth muscle cells was detected by Transwell assay.The apoptosis of vascular smooth muscle cells was detected by TUNEL assay and flow cytometry.The mRNA expression levels of NLRP3 and caspase-1 were detected by qPCR.Western blot assay was utilized to detect NLRP3,caspase-1,and cleaved N-terminal GSDMD protein expression levels. RESULTS AND CONCLUSION:Compared with the control group,the migration ability and apoptosis rate of vascular smooth muscle cells in interferon-γ group were significantly increased(P<0.05).Compared with the control group,the mRNA expression levels of NLRP3 and caspase-1 in vascular smooth muscle cells of interferon-γ group were significantly increased(P<0.05).Compared with control group,the expression levels of NLRP3,caspase-1,and cleaved N-terminal GSDMD protein in vascular smooth muscle cells in the interferon-γ group were significantly increased(P<0.05).The results suggest that interferon-γ may regulate the migration and apoptosis of vascular smooth muscle cells through NLRP3/caspase-1/GSDMD pyroptosis pathway.

Objective To improve the efficiency and accuracy of videonystagmography calibration test results while enabling effective recognition of saccadic undershoot waveform by developing a dual-stream architecture-based deep learning model. Methods A vestibular function calibration test recognition model with cross-modal feature fusion was constructed by integrating vision transformer (ViT) and a modified ConvNeXt convolutional network. The model utilized trajectory pictures and spatial distribution maps as inputs, employed a multi-task learning framework to classify calibration data, and to directly evaluate undershoot waveform. Results The model showed outstanding performance in assessing calibration compliance. The accuracy, sensitivity, specificity of the model in left side, middle, and right side were all greater than 90%, and AUC values were all greater than 0.99, with 97.66% of optimal accuracy (middle), 98.98% of optimal sensitivity (middle), 96.87% of optimal specificity (right side), and 0.997 of AUC (right side). The model also showed promising performance in undershoot waveform recognition with 87.50% of accuracy, 89.66% of sensitivity, 85.71% of specificity, 86.67% of F1 score, and 0.931 of AUC. Conclusions The proposed method not only significantly enhances the efficiency and accuracy of calibration test results, but also provides a novel solution for undershoot waveform recognition.

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: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

BACKGROUND:Palmar locking plate fixation is the most commonly used fixation method for distal radius fractures.However,when the fracture line involves the dorsal articular surface,palmar plate fixation carries a higher risk of postoperative displacement of the dorsal bone mass,especially the dorsal sigmoid notch bone mass. OBJECTIVE:To analyze the fracture line characteristics of distal radius fracture involving the dorsal articular surface,and further investigate the risk factors of postoperative displacement of the dorsal bone mass involving the sigmoid notch,so as to provide evidence for improving the success rate of surgery. METHODS:Retrospective analysis was performed on patients with distal radius fracture who were admitted to Third Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2021 to September 2022.The number of dorsal fractures of the distal radius of 1,2,3 and above was divided into types Ⅰ,Ⅱ,and Ⅲ based on preoperative CT images.The fracture line maps were drawn respectively to analyze the morphological characteristics of the dorsal fracture lines.Patients with dorsal sigmoid notch fracture were followed up for more than 3 months and divided into displaced group and non-displaced group according to whether the dorsal sigmoid notch bone mass displacement occurred after surgery.Age,sex,preoperative and postoperative CT anatomical parameters were compared between the two groups. RESULTS AND CONCLUSION:(1)145 patients with type C of AO/OTA involving the dorsal articular surface were analyzed by fracture line map.According to the number of dorsal fractures,there were 25 cases of type Ⅰ fracture(17.2％),82 cases of type Ⅱ fracture(56.6％),and 38 cases of type Ⅲ fracture(26.2％).Fracture line map showed that the fracture line of type Ⅰ fracture block mainly involved sigmoid notch;type Ⅱ mainly involved sigmoid notch and lister tubercle,and type Ⅲ involved sigmoid notch,lister tubercle,and dorsal radial column.Among the 145 patients,86.2％(125/145 cases)were involved in sigmoid notch,of which type Ⅲ was involved as high as 94.7％(36/38 cases);type Ⅱ was involved as high as 88.0％(72/82 cases),and type Ⅰ was involved as high as 68％(17/25 cases).(2)76 cases of type C of AO/OTA involving the dorsal sigmoid notch were included for further study,of which 65 cases were not displaced after operation and 11 cases were displaced.In univariate analysis,there were no statistically significant differences between the two groups in age,sex,injury site,preoperative CT dorsal sigmoid notch bone mass length(d1),ulnar length(d2),dorsal height of dorsal sigmoid notch bone mass(d4),and ulnar edge distance between steel plate and radius(d5)(P>0.05).The proportion of dorsal sigmoid notch involving the radioulnar joint:[d2/(d2+d3)],the proportion of articular surface of dorsal sigmoid notch(s1/s2),the distance between the ulnar screw tail and the edge of dorsal sigmoid notch(d6),and the number of screw fixation of dorsal sigmoid notch were statistically significant(P<0.05).(3)Multivariate Logistic regression analysis showed that the number of screw fixation of sigmoid notch was the only risk factor affecting the displacement of sigmoid notch on dorsal ulnar side(P<0.05).(4)It is indicated that type Ⅱ is the most common intra-articular fracture of distal radius involving the back of the radius,followed by type Ⅲ and type Ⅰ with dorsal sigmoid notch bone mass.However,the dorsal sigmoid notch bone mass is prone to postoperative displacement due to the influence of the inferior radioulnar joint ligament,and the fixation of at least one effective screw during the operation can reduce the risk of displacement and help to improve the treatment effect.