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.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Attention deficit hyperactivity disorder(ADHD)is a common childhood neurodevelopmental disorders.In recent years,some studies have shown that there is a high comorbidity between ADHD and childhood allergic diseases such as bronchial asthma,atopic dermatitis,allergic rhinitis,and food allergies.Inflammatory reactions caused by allergic diseases may affect central nervous system function,Thereby further affecting the occurrence and development of ADHD,suggesting that there may be a close connection between the two diseases at the neuro-immune level.Although the common pathogenesis and causal relationship between the two have not been fully elucidated,multiple studies have revealed the epidemiological association between them.This article provides a review of the research on the association between children's allergic diseases and ADHD,and explores the possible comorbid mechanisms between them,and explore the treatment of comorbidities of allergic diseases and ADHD,aiming to provide new ideas for further clinical diagnosis,treatment,and research.In addition,more attention needs to be paid to the importance of prevention.By strengthening children's health education and raising the health awareness of parents and teachers,it can help reduce the risk of illness in children and build a more comprehensive and solid protective barrier for their health.

Objective To investigate the mechanism of circadian clock protein Bmal1(Bmal1)on renal injury with chronic periodontitis,we established an experimental rat periodontitis model.Methods Twelve male Wistar rats were randomly divided into control and periodontitis groups(n=6,each group).The first maxillary molars on both sides of the upper jaw of rats with periodontitis were ligated by using orthodontic ligature wires,whereas the control group re-ceived no intervention measures.After 8 weeks,clinical periodontal parameters,including probing depth,bleeding index,and tooth mobility,were evaluated in both groups.Micro-CT scanning and three-dimensional image recon-struction were performed on the maxillary bones of the rats for the assessment of alveolar bone resorption.Histopatholo-gical observations of periodontal and renal tissues were conducted using hematoxylin-eosin(HE)and periodic acid-Schiff(PAS)staining.Renal function indicators,such as creatinine,albumin,and blood urea nitrogen levels,and oxida-tive stress markers,including superoxide dismutase,glutathione,and malondialdehyde levels,were measured using bio-chemical assay kits.MitoSOX red staining was used to detect reactive oxygen species(ROS)content in the kidneys.The gene and protein expression levels of Bmal1,nuclear factor erythroid 2-related factor 2(Nrf2),and heme oxygenase-1(HO-1)in rat renal tissues were assessed using real-time quantitative polymerase chain reaction(RT-qPCR)and immuno-histochemical staining.Results Micro-CT and HE staining results showed significant bone resorption and attachment loss in the maxillary first molar region of the periodontitis group.Histological examination through HE and PAS staining revealed substantial histopathological damage to the renal tissues of the rats in the periodontitis group.The findings of the assessment of renal function and oxidative stress markers indicated that the periodontitis group exhibited abnormal levels of oxidative stress,whereas the renal function levels showed abnormalities without statistical significance.Mito-SOX Red staining results showed that the content of ROS in the renal tissue of the periodontitis group was significantly higher than that of the control group,and RT-qPCR and immunohistochemistry results showed that the expression levels of Bmal1,Nrf2,and HO-1 in the renal tissues of the rats in the periodontitis group showed a decreasing trend.Conclu-sion Circadian clock protein Bmal1 plays an important role in the oxidative damage process involved in the renal of rats with periodontitis.

Objective This study aims to explore changes in uncoupling protein 2(UCP2)in experimental periodonti-tis-associated renal injury induced by ligation and investigate the effect of UCP2 on renal injury induced by periodontitis.Methods Twelve Wistar male rats were randomly divided into two groups:control and periodontitis groups.A periodon-tal model was built by ligating the maxillary first molars area with 0.2 mm orthodontic ligature wire.After 8 weeks,the in-traoral condition of the rats was observed and periodontal clinical indices such as gingival bleeding index(BI),periodontal probing depth(PD),and tooth mobility(TM)were detected.The maxillary bone was scanned by Micro CT to observe the alveolar bone resorption.The tissue mineral density(TMD),bone mineral density(BMD),bone volume fraction(BV/TV),trabecular thickness(Tb.Th),trabecular bone separation(Tb.Sp)were recorded,and the distance from the enamel bone boundary to the alveolar crest(CEJ-ABC)of the maxillary first molar was measured.The oxidative stress indexes such as malondialdehyde,glutathione(GSH),and superoxide dismutase(SOD)were detected using frozen rat kidney tissue.The gene expression of UCP2,nuclear factor erythroid 2-related factor 2(Nrf2),and peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α)was observed by quantitative real-time polymerase chain reaction(qRT-PCR)test.The gingival tissue of the rats was used for immunohistochemical staining to observe the expression of the UCP2 protein.The fixed rat kidney tissue was used for hematoxylin-eosin(HE),periodic acid-schiff(PAS),MitoSOX Red,JC-1,and immu-nohistochemical staining to observe the renal histopathology,the level of reactive oxygen species(ROS),the level of mito-chondrial membrane potential,and the expression of UCP2,Nrf2,and PGC-1α protein.Rat serum was collected to detect renal function indices,namely,blood urea nitrogen(BUN),creatinine(Cre),and albumin(Alb).Results Compared with the control group,the periodontitis group showed red,swollen,and soft gingival tissue,with gingival probing bleeding,periodontal PD increased,tooth loosening,alveolar bone resorption,decreased TMD,BMD,BV/TV,and Tb.Th indices,and increased Tb.Sp index,CEJ-ABC,and gingival UCP2 protein expression.Compared with the control group,the levels of MDA and ROS in the kidney tissue of periodontitis rats and the gene and protein expression of UCP2 increased,and the levels of MMP,GSH,and SOD and the gene and protein expression of Nrf2 and PGC-1α decreased.Renal functional indi-ces,namely,BUN,Cre,and Alb,were not significantly different between the two groups.Conclusion UCP2 may play a role in renal injury induced by periodontitis through oxidative stress.