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: 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.

[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

Objective:This study aim to explore the distribution patterns of inhalant allergen specific immunoglobulin E(sIgE) positive rates in children with respiratory diseases and its correlation with clinical characteristics, so as to provide reference basis for the prevention and diagnosis of respiratory diseases in children.Methods:A cross-sectional retrospective study was conducted using clinical data from 3 574 children with respiratory tract infections and allergic diseases attending Hunan Children′s Hospital from August 2022 to August 2024.The χ 2 test or Fisher′s test was used for statistical analysis to compare the distribution characteristics of inhaled allergen positive rates among children across different ages, genders, seasons, and diseases. The correlation between allergens and clinical features was analyzed. Results:Of the 3 574 children, 51.4%(1 838) were positive for at least 1 inhalant allergen sIgE, with house dust mite, dust mite, and house dust being the most common allergens with top 3 positive rates. The children had a single sensitization rate of 17.9%(329/1 838) and a multiple sensitization rate of 82.1%(1 509/1 838), with a predominance of two (31.6%, 580/1 838) and three (30.6%, 562/1 838) positive allergens. The total positive rate of allergen sIgE for children in the adolescent group was 70.1%(103/147), higher than that in children in the infant group 24.9%(122/489), the preschool group 49.0%(818/1 669), and the school-age group 62.6%(795/1 269)(all P<0.001). The positive rate of allergen sIgE increased gradually with age (χ 2 trend value=93.70, P<0.001). The overall positive rate of allergen sIgE was higher in male children 52.6%(1 157/2 199) than in female children 49.0%(673/1 375)(χ 2=5.95, P<0.05). The allergic rhinitis subgroup had the highest sIgE positive rate of 60.3%(152/252), followed by the 54.9%(123/224) from the allergic rhinitis with asthma subgroup, and the 52.6%(1 142/2 173) from the asthma subgroup. These differences were statistically significant (χ 2=9.87, P<0.05). The allergen sIgE positive rate of the children was the highest in summer, with 57.8%(786/1 360), and the lowest in winter, with 42.1%(215/511). The difference between the different seasons was statistically significant (χ 2=58.20, P<0.001). Spearman correlation analysis found that the number of positive species of allergens was positively correlated with the sIgE levels ( r=0.51, P<0.001), and there was a positive correlation between sIgE levels of house dust mites and dust mites ( r=0.88, P<0.01). Conclusions:The main allergens of respiratory diseases in children are house dust mite and dust mite. The positive rate of allergen sIgE increases with age, is higher in males than females, has the highest rate of sensitization in summer, and is easy to be multiple sensitized. Early sIgE screening is recommended to guide the prevention and diagnosis of the disease for children.

Objective:This study aim to explore the distribution patterns of inhalant allergen specific immunoglobulin E(sIgE) positive rates in children with respiratory diseases and its correlation with clinical characteristics, so as to provide reference basis for the prevention and diagnosis of respiratory diseases in children.Methods:A cross-sectional retrospective study was conducted using clinical data from 3 574 children with respiratory tract infections and allergic diseases attending Hunan Children′s Hospital from August 2022 to August 2024.The χ 2 test or Fisher′s test was used for statistical analysis to compare the distribution characteristics of inhaled allergen positive rates among children across different ages, genders, seasons, and diseases. The correlation between allergens and clinical features was analyzed. Results:Of the 3 574 children, 51.4%(1 838) were positive for at least 1 inhalant allergen sIgE, with house dust mite, dust mite, and house dust being the most common allergens with top 3 positive rates. The children had a single sensitization rate of 17.9%(329/1 838) and a multiple sensitization rate of 82.1%(1 509/1 838), with a predominance of two (31.6%, 580/1 838) and three (30.6%, 562/1 838) positive allergens. The total positive rate of allergen sIgE for children in the adolescent group was 70.1%(103/147), higher than that in children in the infant group 24.9%(122/489), the preschool group 49.0%(818/1 669), and the school-age group 62.6%(795/1 269)(all P<0.001). The positive rate of allergen sIgE increased gradually with age (χ 2 trend value=93.70, P<0.001). The overall positive rate of allergen sIgE was higher in male children 52.6%(1 157/2 199) than in female children 49.0%(673/1 375)(χ 2=5.95, P<0.05). The allergic rhinitis subgroup had the highest sIgE positive rate of 60.3%(152/252), followed by the 54.9%(123/224) from the allergic rhinitis with asthma subgroup, and the 52.6%(1 142/2 173) from the asthma subgroup. These differences were statistically significant (χ 2=9.87, P<0.05). The allergen sIgE positive rate of the children was the highest in summer, with 57.8%(786/1 360), and the lowest in winter, with 42.1%(215/511). The difference between the different seasons was statistically significant (χ 2=58.20, P<0.001). Spearman correlation analysis found that the number of positive species of allergens was positively correlated with the sIgE levels ( r=0.51, P<0.001), and there was a positive correlation between sIgE levels of house dust mites and dust mites ( r=0.88, P<0.01). Conclusions:The main allergens of respiratory diseases in children are house dust mite and dust mite. The positive rate of allergen sIgE increases with age, is higher in males than females, has the highest rate of sensitization in summer, and is easy to be multiple sensitized. Early sIgE screening is recommended to guide the prevention and diagnosis of the disease for children.

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Objective To explore the effect of training mode based on action learning on improving the practicing ability of hospital pharmacists.Methods Thirty pharmacists who received training from September 2022 to December 2023 at Panzhihua Central Hospital were randomly divided into an education reform group(16 cases)and a routine group(14 cases).The education reform group adopted a routine teaching method based on action learning,while the routine group adopted a routine teaching method.The differences between the two groups of pharmacists in theoretical knowledge,practical operation,pharmaceutical services,emergency response,and comprehensive quality were compared.Results The pharmacists in the education reform group were better than the routine group in prescription review,clinical medication analysis,pharmaceutical services,emergency response,andcomprehensive quality.The difference was statistically significant(P＜0.05).Conclusion The teaching model based on action learning can effectively enhance the higher order thinking ability of pharmacists and help them better apply medical knowledge and skills to serve patients and physicians.

Objective:To determine the incidence of adrenal incidentalomas(AIs) in patients with diabetes mellitus and the metabolism profiles.Methods:A total of 615 hospitalized patients with diabetes mellitus in the Department of Endocrinology and Metabolism of Peking University People′s Hospital from March 2020 to May 2021 were retrospectively included in this study. AIs were screened by unenhanced chest computed tomography(CT) retrospectively and subsequently confirmed by multiplanar reconstruction. Participants′ physical indicators, metabolic profiles, and adrenal function parameters were collected. Unpaired t test, Mann-Whitney U test, and Chi-Square test were adopted to compare the metabolism profiles between diabetes mellitus patients with or without AIs. Regression models were used to estimate the correlations between AIs and the metabolism profiles such as blood glucose, blood lipids, blood pressure, and the adrenal function parameters.Results:Twenty-seven out of 615 participants were detected with AIs(4.4%). Patients with AIs had higher body mass index, waist circumference, and hip circumference than patients without AIs [(29.4±5.1)kg/m 2vs(26.8±3.8)kg/m 2,P=0.018; (102.3±11.7)cm vs(95.8±10.3)cm, P=0.002; (107.3±10.1)cm vs(101.4±7.6)cm, P=0.008]. The levels of serum uric acid and urinary albumin/creatinine ratio were also significantly increased in patients with AIs [(409.6±118.1)μmol/L vs(357.4±100.6)μmol/L, P=0.009; 21.25(7.49, 180.24)mg/g vs 8.60(4.71, 34.56)mg/g, P=0.010]. Besides, individuals with AIs were also associated with a higher risk of co-existing hypertension( P=0.045). Conclusion:The incidence of AIs in patients with diabetes is 4.4%. The presence of AIs in patients with diabetes may associated with increased risk of obesity and hypertension.