Objective:To explore the clinical characteristics and genetic etiology of a child with Oral-facial-digital syndrome type Ⅰ(OFDSⅠ).Method:A child with OFDSⅠ who received treatment at the Women and Children′s Hospital Affiliated to Ningbo University in March 2023 was selected as the study subject. A retrospective research method was used to collect the clinical data of the child. Peripheral venous blood samples were collected from the child, her parents and sister. Genomic DNA was extracted, and whole exome sequencing (WES) was performed. Candidate variants were validated using Sanger sequencing for familial verification. According to the Standards and Guidelines for the Interpretation of Sequence Variants developed by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the " ACMG Guidelines" ), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Ningbo University Affiliated Women and Children′s Hospital (Ethic No.: EC 2024-063).Results:The child was a prematurely born female with deformities of the oral cavity, fingers, and toes. She was admitted to the Neonatal Department of the Hospital where she was born due to shortness of breath 15 minutes after birth. The WES results indicated that the child has harbored a heterozygous c. 710dup(p.Y238Vfs*2) frameshifting variant of the OFD1 gene. Sanger sequencing confirmed that neither of the child′s parents nor her sister had carried the same variant. According to the ACMG guidelines, the variant was rated as pathogenic (PVS1+ PS4_Moderate+ PM2-Supporting+ PM6_Supporting+ PP4). Conclusion:Children with OFDSⅠ have clinical features such as oral, finger, and toe deformities. The c. 710dup(p.Y238Vfs*2) variant of the OFD1 gene probably underlay the OFDSⅠ in this child. Above result has enriched the mutational spectrum of the OFD1 gene.

Objective:To understand the molecular evolutionary characteristics of the recombinant strain GII.3[P12] of norovirus acute gastroenteritis outbreaks and aggregated outbreaks in China from 2022 to 2023.Methods:Epidemiological information, case information, clinical samples, as well as detection and genotyping information of norovirus outbreaks and aggregated outbreaks from 2022 to 2023 were collected; positive samples of the GII.3[P12] recombinant strain were subjected to nucleic acid extraction, whole-genome amplification, and sequence analysis; and homology simulation method were used to construct a three-dimensional structure and predict antigenic epitopes.Results:From January 2022 to December 2023, a total of 1 136 norovirus outbreaks and aggregated outbreaks were reported in China′s norovirus outbreak surveillance network, and genotyping result were successfully obtained for 942 outbreaks, with GII dominating, accounting for 76.0% (716/942), and the proportion of GI and mixed genotypes being 15.8% (149/942) and 8.2% (77/942). Norovirus outbreaks caused by GII were dominated by GII.3[P12] (22.5%, 161/716), while other major genotypes included GII.17[P17] (18.7%, 134/716), GII.4_Sydney 2012[P16] (11.6%, 83/716) and GII.6[P7] ( 11.3%, 81/716). 2022-2023 Outbreaks caused by GII.3[P12] were concentrated in February-March (54.0%, 87/161), with the main outbreaks occurring in nursery and primary schools (87.5%), the mode of transmission was mainly human-to-human (68.9%), and the main susceptible population was children aged 3-7 years (93.3%). In this study, the genome sequences of 25 GII.3[P12] recombinant strains were obtained, and according to the phylogenetic analysis, it was shown that the GII.3[P12] recombinant strains in China in 2022-2023 belonged to the Cluster IV cluster of sublineage b (7 strains) and sublineage c (18 strains). A total of 11 linear and 8 conformational epitopes were predicted by epitope prediction analysis, and the predicted linear and conformational epitopes had overlapping positions, and each conformational epitope was part of the predicted linear epitope with conserved potential antigen-binding and receptor-binding sites.Conclusions:The recombinant strain GII.3[P12] is one of the epidemic strains that will cause outbreaks and clusters of norovirus in China in 2022-2023, and its genome did not undergo significant mutation.

Objective:To analyze the current status and trends in the clinical management and outcomes of respiratory distress syndrome (RDS) in preterm infants <32 weeks′ gestation admitted to the Chinese Neonatal Network (CHNN) from 2019 to 2023.Methods:A cross-sectional study was conducted from November 2024 to January 2025 using the CHNN cohort of very preterm and extremely preterm infants. A total of 30 869 RDS infants with gestational age <32 weeks were admitted within 1 day after birth to CHNN centers from 2019 to 2023. Data on demographics, perinatal management, early complications within 7 days of age, and in-hospital outcomes were collected. Yearly groups were defined by admission year. Trends by year were evaluated by Cochran-Armitage trend test, linear regression model and median regression model.Results:The gestational age at birth of 30 869 RDS infant was 28.9 (27.1, 30.7) weeks and the birth weight was 1 259 (932, 1 586) g. Males account for 56.5% (17 363/30 757). From 2019 to 2023, the prevalence of RDS was 73.8% (5 503/7 461), 74.5% (5 490/7 368), 79.8% (5 884/7 372), 81.6% (6 435/7 889), and 86.0% (7 557/8 789), respectively, showing an increasing trend year by year ( P<0.001). The overall rate of pulmonary surfactant administration was 72.4% (22 359/30 869), fluctuating between 71.2% (5 381/7 557) and 74.3% (4 089/5 503) over the 5-year period. Antenatal corticosteroids were administered to 82.3% (24 357/29 597) mothers of RDS infants and 23.6% (7 218/30 565) RDS infants received noninvasive positive end-expiratory pressure support in the delivery room, both showing a increasing trend over the 5 years (both P<0.001). The incidence of pneumothorax and the use rate of inhaled nitric oxide within 7 days of age were 1.3% (393/30 846) and 1.4% (436/30 869), respectively, both showing increasing trends over the 5 years (both P<0.001). The rate of complete course of antenatal corticosteroids administration was 64.6% (14 458/22 382), the rates of discharge against medical advice and mortality within 7 days of age were 5.3% (1 635/30 869) and 2.7% (724/26 803), respectively, all showing a decreasing trend over time (all P<0.05). Regarding in-hospital outcomes, mortality rate of RDS infants was 4.6% (1 228/26 803), showing a downward trend year by year ( P=0.005). The incidence of bronchopulmonary dysplasia (BPD) was 35.0% (9 417/26 919), and the combined incidence of death or BPD was 36.4% (9 763/26 803), both showing an increasing trend year by year (both P<0.001). Conclusions:RDS prevalence increased annually in preterm infants <32 weeks′ gestation from 2019 to 2023, with declining mortality but rising BPD rates. While antenatal steroid use and noninvasive positive end-expiratory pressure support application improved, full-course antenatal steroid compliance decreased. These findings highlight the need for standardized perinatal management protocols to improve the clinical management of RDS.

Objective:To examine the near-complete genomic analysis of norovirus (NoV) subtype GⅡ.17 [P17] outbreaks in Beijing Chaoyang District from 2014 to 2024.Methods:Data and specimens related to outbreaks of the NoV aggregation in Beijing′s Chaoyang District from 2014 to 2024 were collected. The NoV was identified using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). Specimens with positive nucleic acid were amplified by standard PCR, whole genome sequencing and evolutionary analysis. Amino acid site variations were compared.Results:In Chaoyang District, from 2014 to 2024, a total of 637 aggregated outbreaks caused by the NoV infection were reported, of which 584 were successfully typed. The epidemic caused by the GⅡ.17 [P17] subtype accounted for 8.79% (56/637), which was the dominant epidemic gene subtype in 2014-2015, sporadic in 2016-2019, reappeared in 2022, and significantly increased in 2024 (27.27%, 24/88). Outbreaks caused by the GⅡ.17 [P17] subtype occurred mainly from October to December, with the main sites of occurrence in primary schools and kindergartens. This study yielded 53 near-complete genome sequences of the GⅡ.17 [P17] subtype from 46 incidents in Chaoyang District. The GⅡ.17 [P17] subtype sequences of Chaoyang District from 2014 to 2024 were segmented into three subgroups on the evolutionary tree, with sequences from 2014 to 2019, 2022 to April 2024, and May to December 2024 clustered into the d, e, and b subgroups, respectively. In the VP1 region′s P2 area, particularly at the HBGA binding site, subgroups b and e exhibited mutations in 22 and two sites, while subgroups b and e showed mutations in four and one sites, predominantly in the RdRp region.Conclusion:The outbreak caused by the NoV GⅡ.17 [P17] subtype in Chaoyang District from 2014 to 2024 continues, with a significant increase in 2024, and it becomes the dominant gene subtype from October to December. The sequence formation of the NoV GⅡ.17 [P17] subtype in Chaoyang District from January to April 2022 and from May to December 2024 shows two different evolutions, with specific mutation sites, requiring continuous monitoring of the NoV GⅡ.17 [P17] subtype.

Objective:To investigate the protective mechanism of cerium oxide nanoparticles(CeO2 NPs)against acute pancreatitis(AP),with a focus on their antioxidant and anti-inflammatory properties.Methods:CeO2 NPs were characterized by transmission elec-tron microscopy(TEM)and dynamic light scattering.In in vitro experiments,cell counting Kit-8(CCK-8)assay,flow cytometry,and Western blotting were used to validate the role of CeO2 NPs in preventing the apoptosis of pancreatic acinar cells.In in vivo experi-ments,C57BL/6 mice were divided into control group,AP group,AP+CeO2 group,SAP group,and SAP+CeO2 group to investigate the mechanism of action of CeO2 NPs in alleviating inflammation and oxidative stress in AP mice.Results:CeO2 NPs demonstrated rela-tively good stability and biocompatibility,with a particle size of(50±4)nm on TEM.In vitro experiments showed that CeO2 NPs sig-nificantly reduced the apoptosis of pancreatic acinar cells by alleviating lipid peroxidation and maintaining mitochondrial membrane potential.In vivo experiments showed that CeO2 NPs could reduce the serum levels of amylase,lipase,and inflammatory cytokines(in-terleukin-6 and tumor necrosis factor-α).This result might be related to the regulation of the IKK/P53/Bcl-2 pathway.CeO2 NPs re-duced the production of reactive oxygen species and enhanced anti-oxidant response by regulating the Nrf-2 signaling pathway.Con-clusion:CeO2 NPs exert anti-inflammatory and antioxidant effects by regulating the IκB kinase/tumor protein p53/B-cell lymphoma 2(IKK/P53/bcl-2)and nuclear factor erythroid 2-related(Nrf-2)signaling pathways,thereby showing promising potential for the treatment of AP.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Oral-facial-digital syndrome type Ⅰ(OFDSⅠ). METHODS: A child with OFDSⅠ who received treatment at the Women and Children's Hospital Affiliated to Ningbo University in March 2023 was selected as the study subject. A retrospective research method was used to collect the clinical data of the child. Peripheral venous blood samples were collected from the child, her parents and sister. Genomic DNA was extracted, and whole exome sequencing (WES) was performed. Candidate variants were validated using Sanger sequencing for familial verification. According to the Standards and Guidelines for the Interpretation of Sequence Variants developed by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the "ACMG Guidelines"), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Ningbo University Affiliated Women and Children's Hospital (Ethic No.: EC 2024-063). RESULTS: The child was a prematurely born female with deformities of the oral cavity, fingers, and toes. She was admitted to the Neonatal Department of the Hospital where she was born due to shortness of breath 15 minutes after birth. The WES results indicated that the child has harbored a heterozygous c.710dup (p.Y238Vfs*2) frameshifting variant of the OFD1 gene. Sanger sequencing confirmed that neither of the child's parents nor her sister had carried the same variant. According to the ACMG guidelines, the variant was rated as pathogenic (PVS1+PS4_Moderate+PM2-Supporting+PM6_Supporting+PP4). CONCLUSION Children with OFDSⅠ have clinical features such as oral, finger, and toe deformities. The c.710dup (p.Y238Vfs*2) variant of the OFD1 gene probably underlay the OFDSⅠ in this child. Above result has enriched the mutational spectrum of the OFD1 gene.
Humans ; Female ; Orofaciodigital Syndromes/genetics* ; Exome Sequencing ; Retrospective Studies ; Mutation ; Child ; Proteins

The National Essential Medicines System could protect public health and ensure access to essential medications.Although the current selection methods for China's National Essential Medicines Lists(NEMLs)are becoming more scientific and standardized,there are still problems such as much emphasis on expert experience and the lack of transparency of decision-making basis.To address these issues,it proposes an evidence-based decision-making pathway for NEMLs selection guided by clinical value.This approach ensures a strong integration of evidence and decision-making,offering valuable insights for improving the adjustment procedures and selection criteria of the NEMLs in China.

Objective:To examine the near-complete genomic analysis of norovirus (NoV) subtype GⅡ.17 [P17] outbreaks in Beijing Chaoyang District from 2014 to 2024.Methods:Data and specimens related to outbreaks of the NoV aggregation in Beijing′s Chaoyang District from 2014 to 2024 were collected. The NoV was identified using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). Specimens with positive nucleic acid were amplified by standard PCR, whole genome sequencing and evolutionary analysis. Amino acid site variations were compared.Results:In Chaoyang District, from 2014 to 2024, a total of 637 aggregated outbreaks caused by the NoV infection were reported, of which 584 were successfully typed. The epidemic caused by the GⅡ.17 [P17] subtype accounted for 8.79% (56/637), which was the dominant epidemic gene subtype in 2014-2015, sporadic in 2016-2019, reappeared in 2022, and significantly increased in 2024 (27.27%, 24/88). Outbreaks caused by the GⅡ.17 [P17] subtype occurred mainly from October to December, with the main sites of occurrence in primary schools and kindergartens. This study yielded 53 near-complete genome sequences of the GⅡ.17 [P17] subtype from 46 incidents in Chaoyang District. The GⅡ.17 [P17] subtype sequences of Chaoyang District from 2014 to 2024 were segmented into three subgroups on the evolutionary tree, with sequences from 2014 to 2019, 2022 to April 2024, and May to December 2024 clustered into the d, e, and b subgroups, respectively. In the VP1 region′s P2 area, particularly at the HBGA binding site, subgroups b and e exhibited mutations in 22 and two sites, while subgroups b and e showed mutations in four and one sites, predominantly in the RdRp region.Conclusion:The outbreak caused by the NoV GⅡ.17 [P17] subtype in Chaoyang District from 2014 to 2024 continues, with a significant increase in 2024, and it becomes the dominant gene subtype from October to December. The sequence formation of the NoV GⅡ.17 [P17] subtype in Chaoyang District from January to April 2022 and from May to December 2024 shows two different evolutions, with specific mutation sites, requiring continuous monitoring of the NoV GⅡ.17 [P17] subtype.

The National Essential Medicines System could protect public health and ensure access to essential medications.Although the current selection methods for China's National Essential Medicines Lists(NEMLs)are becoming more scientific and standardized,there are still problems such as much emphasis on expert experience and the lack of transparency of decision-making basis.To address these issues,it proposes an evidence-based decision-making pathway for NEMLs selection guided by clinical value.This approach ensures a strong integration of evidence and decision-making,offering valuable insights for improving the adjustment procedures and selection criteria of the NEMLs in China.

Objective:To explore the clinical characteristics and genetic etiology of a child with Oral-facial-digital syndrome type Ⅰ(OFDSⅠ).Method:A child with OFDSⅠ who received treatment at the Women and Children′s Hospital Affiliated to Ningbo University in March 2023 was selected as the study subject. A retrospective research method was used to collect the clinical data of the child. Peripheral venous blood samples were collected from the child, her parents and sister. Genomic DNA was extracted, and whole exome sequencing (WES) was performed. Candidate variants were validated using Sanger sequencing for familial verification. According to the Standards and Guidelines for the Interpretation of Sequence Variants developed by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the " ACMG Guidelines" ), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Ningbo University Affiliated Women and Children′s Hospital (Ethic No.: EC 2024-063).Results:The child was a prematurely born female with deformities of the oral cavity, fingers, and toes. She was admitted to the Neonatal Department of the Hospital where she was born due to shortness of breath 15 minutes after birth. The WES results indicated that the child has harbored a heterozygous c. 710dup(p.Y238Vfs*2) frameshifting variant of the OFD1 gene. Sanger sequencing confirmed that neither of the child′s parents nor her sister had carried the same variant. According to the ACMG guidelines, the variant was rated as pathogenic (PVS1+ PS4_Moderate+ PM2-Supporting+ PM6_Supporting+ PP4). Conclusion:Children with OFDSⅠ have clinical features such as oral, finger, and toe deformities. The c. 710dup(p.Y238Vfs*2) variant of the OFD1 gene probably underlay the OFDSⅠ in this child. Above result has enriched the mutational spectrum of the OFD1 gene.