Objective:To explore the genotype-phenotype relationship in a child with Opitz G/BBB syndrome (OS) with mild clinical phenotype.Methods:A child with motor developmental delay as the initial symptom admitted to Xi ′an Children′s Hospital on June 10, 2021 was selected for this study. Clinical data were collected, and peripheral blood samples were obtained from the child and his mother. Whole exome sequencing (WES) was performed to identify genetic variant in the child. Candidate variant were verified by Sanger sequencing to assess inheritance patterns and pathogenicity. Real-time fluorescence quantitative PCR (RT-qPCR) and Western blot (WB) analyses were conducted to evaluate the effects of the variant on mRNA and protein expression, respectively, using recombinant expression plasmids generated in vitro. This study was approved by the Medical Ethics Committee of Xi′an Children′s Hospital (Ethics No. 20240045).Results:① The child, a 9-month-and-7-day-old boy, presented with a low nasal bridge, hypertelorism, and difficulty sitting independently. Echocardiography revealed an atrial septal defect. ② WES identified a homozygous variant in the MIDI gene, c. 1483C>T (p.R495X), which was confirmed by Sanger sequencing and found to be inherited from the mother.③ Recombinant expression plasmids were successfully constructed. RT-qPCR analysis showed that the variant significantly reduced MIDI gene mRNA expression, while WB results indicated that the variant led to the production of a truncated protein. Conclusion:The mild clinical phenotype of OS in this child may be attributed to the mRNA degradation escape mechanism induced by the nonsense variant c. 1483C>T(p.R495X) in the MIDI gene. These findings provide valuable diagnostic insights for this pedigree and contribute to the understanding of the genotype-phenotype correlation in OS.

Objective:To evaluate the effectiveness and safety of zoledronic acid in patients with Paget′s disease of bone based on clinical data from a single medical center.Methods:This retrospective study included 24 patients diagnosed with Paget′s disease of bone and treated with zoledronic acid at Peking Union Medical College Hospital between January 2009 and June 2020. Demographic data, clinical symptoms, treatment efficacy, and safety outcomes were collected. The primary efficacy measure was serum alkaline phosphatase(ALP) levels. Treatment was considered effective if ALP levels returned to normal or decreased by more than 75% from baseline in the difference between the ALP level and its normal median value.Results:Among the 24 patients with Paget′s bone disease, the most commonly affected site was the skull(in 17 cases). All patients received a single 5 mg intravenous infusion of zoledronic acid. Serum ALP levels significantly decreased after treatment. Among the 15 patients who completed at least 3 months of follow-up, all achieved treatment success. The median time for serum ALP levels to reach the target was 13.1(9.4, 26.1) weeks. In 12 patients, ALP levels normalized within a medium of 16.9(11.5, 37.3) weeks, and remained stable over a medium follow-up of 4.56(2.42, 5.71) years. The most common side effects were hypocalcemia(21 cases, 87.5%) and flu-like symptoms(17 cases, 70.8%). Seven patients had severe hypocalcemia(serum calcium<1.75 mmol/L), and they had higher baseline levels of ALP, calcium, and phosphorus compared to those with mild hypocalcemia.Conclusions:Zoledronic acid 5 mg intravenous infusion effectively controlled disease activity in patients with Paget′s disease of bone. Generally, Most patients achieved treatment goals within 3-4 months, with sustained remission for a median of 4 years. Hypocalcemia was the most frequent side effect, underscoring the importance of timely calcium and vitamin D supplementation.

Primary hyperparathyroidism(PHPT) is relatively rare in individuals before adulthood. Among juvenile patients, hereditary PHPT accounts for a significant proportion. Specifically, infant and toddler patients often carry gene mutations related to the calcium-sensing receptor signaling pathway, whereas children and adolescent patients predominantly exhibit mutations in genes associated with cell proliferation. Notably, PHPT in infants, children, and adolescents differs significantly from that in adult patients in terms of genetic background, clinical manifestations, treatment strategies, and prognosis. This article aims to systematically summarize the genetic characteristics and clinical features of juvenile-onset PHPT to enhance the physicians' understanding of this disease.

OBJECTIVE: To explore the genotype-phenotype relationship in a child with Opitz G/BBB syndrome (OS) with mild clinical phenotype. METHODS: A child with motor developmental delay as the initial symptom admitted to Xi'an Children's Hospital on June 10, 2021 was selected for this study. Clinical data were collected, and peripheral blood samples were obtained from the child and his mother. Whole exome sequencing (WES) was performed to identify genetic variant in the child. Candidate variant were verified by Sanger sequencing to assess inheritance patterns and pathogenicity. Real-time fluorescence quantitative PCR (RT-qPCR) and Western blot (WB) analyses were conducted to evaluate the effects of the variant on mRNA and protein expression, respectively, using recombinant expression plasmids generated in vitro. This study was approved by the Medical Ethics Committee of Xi'an Children's Hospital (Ethics No. 20240045). RESULTS: The child, a 9-month-and-7-day-old boy, presented with a low nasal bridge, hypertelorism, and difficulty sitting independently. Echocardiography revealed an atrial septal defect. WES identified a homozygous variant in the MIDI gene, c.1483C>T (p.R495X), which was confirmed by Sanger sequencing and found to be inherited from the mother.Recombinant expression plasmids were successfully constructed. RT-qPCR analysis showed that the variant significantly reduced MIDI gene mRNA expression, while WB results indicated that the variant led to the production of a truncated protein. CONCLUSION The mild clinical phenotype of OS in this child may be attributed to the mRNA degradation escape mechanism induced by the nonsense variant c.1483C>T (p.R495X) in the MIDI gene. These findings provide valuable diagnostic insights for this pedigree and contribute to the understanding of the genotype-phenotype correlation in OS.
Humans ; Male ; Infant ; Transcription Factors/metabolism* ; Microtubule Proteins/genetics* ; Craniosynostoses/genetics* ; Hypospadias/genetics* ; Codon, Nonsense/genetics* ; RNA, Messenger/metabolism* ; Female ; RNA Stability/genetics* ; Phenotype ; Nuclear Proteins/genetics* ; Ubiquitin-Protein Ligases ; Esophagus/abnormalities* ; Hypertelorism

This study investigated the effect of small RNA ncBCG201 on the stress adaptation and intracellular survival of Myco-bacterium bovis.Differentially expressed ncRNAs were screened with RNA-seq after BCG infection of THP-1 macrophages.The ncBCG201 overexpression strain was constructed,and its stress survival,growth,biofilm formation,and intracellular survival were assessed.The ncBCG201 strain showed slower growth and earlier entry into stationary phase.Survival significantly increased under car-bon starvation but decreased under membrane pressure.Biofilm formation capability decreased.Intracellular survival in THP-1 macro-phages at 24 h and 48 h was significantly higher than observed in the control.Therefore,ncBCG204 enhances BCG survival within macrophages by modulating stress adaptability.

Objective:To construct a risk prediction model for non-suicidal self-injury (NSSI) in adolescents with mood disorders, providing a basis for identifying and intervening in high-risk patients.Methods:A convenience sampling method was used to retrospectively analyze 724 adolescent patients with mood disorders admitted to the open ward of Qingdao Mental Health Center from January 2019 to July 2023. Patients admitted from January 2019 to December 2022 (641 cases) were randomly divided into a modeling group and an internal validation group in a 7∶3 ratio, while patients admitted from January to July 2023 (83 cases) were used as an external validation group. A binary multivariate logistic regression analysis was used to construct a nomogram prediction model for NSSI risk in adolescents with mood disorders. The predictive performance of the model was evaluated using the area under the curve (AUC), sensitivity, and specificity.Results:There were 179 males and 545 females, aged 15 (14, 17) years old. Among the 724 patients, 449 were in the modeling group, 192 in the internal validation group, and 83 in the external validation group. The incidence of NSSI in the modeling group was 32.96% (148/449). Reduced food intake ( OR=10.980, 95% CI 4.462-27.017), passive contact ( OR=4.681, 95% CI 1.986-11.031), Hamilton Depression Rating Scale-17 score >17 ( OR=12.235, 95% CI 4.657-32.141), Hamilton Anxiety Rating Scale score>15 ( OR=27.888, 95% CI 8.700-124.630), Insomnia Severity Index score >15 ( OR=6.357, 95% CI 2.257-17.899), and higher levels of past self-injury ( OR=1.663, 95% CI 1.428-1.935) were independent risk factors for NSSI in adolescents with mood disorders (all P<0.05). The AUC of the nomogram model based on these six factors was 0.973, with a sensitivity of 0.94 and a specificity of 0.89. Conclusions:The risk prediction model for NSSI in adolescents with mood disorders has good discrimination, accuracy, and practicality, and can help identify high-risk NSSI populations among adolescents with mood disorders.

Objective:To evaluate and integrate the evidence related to the prevention of unplanned readmission in elderly patients with ischemic stroke.Methods:A computerized search was conducted on various guideline websites and databases for clinical decisions, best practices, guidelines, evidence summaries, systematic reviews, and expert consensuses regarding the prevention of unplanned readmission in elderly patients with ischemic stroke. The search period was from the establishment of the databases to August 31, 2024. The literature quality evaluation criteria of the Joanna Briggs Institute Evidence-Based Health Care Centre and so on were used to evaluate the quality of different types of studies.Results:A total of 25 articles were included, consisting of one clinical decision, nine guidelines, six evidence summaries, eight systematic reviews, and one expert consensus. Evidence was integrated from two themes: discharge planning services (including five dimensions: principles, preliminary assessment, comprehensive assessment, plan formulation and implementation, tracking and evaluation) and early functional rehabilitation (including four dimensions: rehabilitation time, rehabilitation plan, rehabilitation intensity, and functional rehabilitation) , forming 39 pieces of best evidence.Conclusions:This study provides an evidence-based basis for the clinical nursing practice of preventing unplanned readmission in elderly patients with ischemic stroke. Evidence users need to select the best evidence according to the clinical reality to promote the smooth transition of patients and reduce the readmission rate.

Objective To systematically evaluate the factors that promote and hinder exercise in frail older adults,and to provide references for the formulation of exercise intervention programs.Methods We searched PubMed,Web of Science,Embase,CINAHL,Cochrane library,CNKI,Wanfang,VIP database,and China Biomedical Literature Database for qualitative studies on exercise facilitators and hindrances in frail older adults,and the search time period was from the establishment of the databases to September 1,2024.The quality of the literature was evaluated using the Joanna Brigg Institute Australian Centre for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research(2016),and the results were integrated by integrating methods.Results A total of 18 studies were included,and 72 research results were extracted,and 10 categories were summarized.The final synthesis included 2 integrated results:the facilitators included personal exercise motivation,physical and psychological benefits,positive interpersonal interactions,multiple social support systems and person-centred exercise programme;the impediments included underlying diseases and somatic functional limitations,negative psychological status,low health literacy,family role conflicts and limits of the environment.Conclusion Exercise for frail older adults is affected by a variety of factors.Healthcare professionals should improve the positive perception of exercise for frail older people and help them overcome psychological barriers;establish an all-round support system to enhance the sense of social contact of the frail elderly;formulate a personalised exercise programme with a human-centred approach to enhance the motivation of the frail elderly.

Objective To systematically evaluate the factors that promote and hinder exercise in frail older adults,and to provide references for the formulation of exercise intervention programs.Methods We searched PubMed,Web of Science,Embase,CINAHL,Cochrane library,CNKI,Wanfang,VIP database,and China Biomedical Literature Database for qualitative studies on exercise facilitators and hindrances in frail older adults,and the search time period was from the establishment of the databases to September 1,2024.The quality of the literature was evaluated using the Joanna Brigg Institute Australian Centre for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research(2016),and the results were integrated by integrating methods.Results A total of 18 studies were included,and 72 research results were extracted,and 10 categories were summarized.The final synthesis included 2 integrated results:the facilitators included personal exercise motivation,physical and psychological benefits,positive interpersonal interactions,multiple social support systems and person-centred exercise programme;the impediments included underlying diseases and somatic functional limitations,negative psychological status,low health literacy,family role conflicts and limits of the environment.Conclusion Exercise for frail older adults is affected by a variety of factors.Healthcare professionals should improve the positive perception of exercise for frail older people and help them overcome psychological barriers;establish an all-round support system to enhance the sense of social contact of the frail elderly;formulate a personalised exercise programme with a human-centred approach to enhance the motivation of the frail elderly.