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.

Obesity has become a chronic non-communicable disease that seriously endangers human health,with nearly half of adults in China suffering from overweight or obesity.Body mass index as the most commonly used measure of obesity in clinical practice,can be used to screen for obesity but cannot define diseases or guide clinical decision-making,and has certain limitations.This article introduces a new obesity staging system:the Edmonton Obesity Staging System,and reviews its applications in bariatric surgeryand other fields,in order to provide effective means for accurate diagnosis and treatment of obese patients.

Objective To explore the relationship between hepatocyte nuclear factor 1A(HNF1A)-associated congenital hyperinsulinism(CHI),HNF1A-maturity-onset diabetes of the young(MODY)and C-reactive protein(C-RP)levels.Methods PubMed,CNKI and Wanfang Data were searched for literature on HNF1A gene mutation published from inception to December 2023,and the genetic and clinical information of HNF1A mutation-related CHI and HNF1A-MODY were extracted.According to the clinical phenotypes,the HNF1A mutation sites included in the literature were divided into the Biphenotypic mutations(Biphenotypic,n=84)group and the DM phenotype-associated mutations(DM,n=378)group.The levels of C-RP and C-P were collected and compared in patients with HNF1A-MODY and T2DM by meta-analysis.Results A total of 9 articles about HNF1A mutation-related CHI were included,and 19 mutation sites were found to be associated with CHI.A total of 143 articles related to HNF1A-MODY were included,and 589 mutation sites were found to be associated with HNF1A-MODY.The age at diagnosis and 2 hPG were significantly lower in the Biphenotypic group than in the DM group(P<0.05).A total of 11 articles were included in the meta-analysis.Compared with T2DM patients,HNF1A-MODY patients had lower C-RP(MD-1.61,95%CI-1.96～-1.26,P<0.05)and lower C-P(MD-0.95,95%CI-1.87～-0.03,P<0.05).Conclusions CHI is an important clinical feature of HNF1A-MODY,and hyperinsulinemia may exist before the decline of islet β cell function.

Evolocumab is a lipid-lowering agent used to reduce low-density lipoprotein cholesterol levels and decrease the all-cause mortality rate of cardiovascular diseases.There are few ocular adverse reactions when the drug is used clinically.This article reports a case of primary angle-closure glaucoma.After three sessions of lipid-lowering treatment with the proprotein convertase subtilisin type 9(PCSK9)inhibitor Evolocumab,the patient developed swelling and pain in the left eye and blurred vision.Ophthalmic examination revealed a significant increase in intraocular pressure in the left eye,suggesting an acute attack of angle-closure glaucoma.After treatment,the intraocular pressure dropped to the normal level.This article discusses this case and reviews relevant literature,suggesting that when using PCSK9 inhibitors in clinical practice,the ocular conditions of patients should be closely monitored,especially for those with risk factors for glaucoma.

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.

In the past decade, real-world data (RWD) research has undergone significant transformations due to data aggregation and processing technologies. However, there is still a lack of consensus regarding the scope of RWD applications and the value of real-world evidence (RWE). This study briefly outlined the origins of the concept of RWD study and its early research scope to promote further development in this area. We also reviewed the understanding of RWD applications and research models from the five perspectives of healthcare professionals, medical institutions, decision-making departments, cross-regional cooperation model, and the practice of the One-Health model. Finally, we systematically summarized the renewed understanding of the value of RWE while looking ahead to the challenges and future developments in this field.

Evolocumab is a lipid-lowering agent used to reduce low-density lipoprotein cholesterol levels and decrease the all-cause mortality rate of cardiovascular diseases.There are few ocular adverse reactions when the drug is used clinically.This article reports a case of primary angle-closure glaucoma.After three sessions of lipid-lowering treatment with the proprotein convertase subtilisin type 9(PCSK9)inhibitor Evolocumab,the patient developed swelling and pain in the left eye and blurred vision.Ophthalmic examination revealed a significant increase in intraocular pressure in the left eye,suggesting an acute attack of angle-closure glaucoma.After treatment,the intraocular pressure dropped to the normal level.This article discusses this case and reviews relevant literature,suggesting that when using PCSK9 inhibitors in clinical practice,the ocular conditions of patients should be closely monitored,especially for those with risk factors for glaucoma.

In the past decade, real-world data (RWD) research has undergone significant transformations due to data aggregation and processing technologies. However, there is still a lack of consensus regarding the scope of RWD applications and the value of real-world evidence (RWE). This study briefly outlined the origins of the concept of RWD study and its early research scope to promote further development in this area. We also reviewed the understanding of RWD applications and research models from the five perspectives of healthcare professionals, medical institutions, decision-making departments, cross-regional cooperation model, and the practice of the One-Health model. Finally, we systematically summarized the renewed understanding of the value of RWE while looking ahead to the challenges and future developments in this field.