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.

Objective To construct a predictive model for cerebral small vessel disease (CSVD) MRI burden based on β2-microglobulin (β2-MG) and lipoprotein(a) [Lp(a)], analyze its predictive value, and validate the model. Methods A total of 138 CSVD patients admitted to Anhui No.2 Provincial People’s Hospital from February 2023 to August 2024 were enrolled. Patients were divided into a low-burden group (n=63) and a moderate/severe burden group (n=75) according to the CSVD MRI burden scoring criteria. The related clinical data were compared between the two groups. Binary logistic regression analysis was used to identify independent factors for CSVD moderate/severe MRI burden. A nomogram predictive model was constructed based on these factors and its performance was evaluated. Results The proportions of male patients, as well as those with a history of diabetes or hypertension, were significantly higher in the moderate/severe burden group than those in the low burden group. Additionally, the age of patients in the moderate/severe burden group was significantly older, and the levels of β2-MG, Lp(a), and homocysteine (Hcy) were higher than those in the low burden group (P＜0.01). Binary logistic regression analysis revealed that hypertension, diabetes, β2-MG, and Lp(a) were independent factors for CSVD moderate/severe MRI burden (P＜0.05). The nomogram predictive model based on these four factors had a cut-off value of 0.467 0, with an area under curve (AUC) of 0.838 7 (95%CI 0.760 8-0.916 6) in the training set (n＝97) and 0.854 1 (95%CI 0.742 1-0.966 1) in the internal validation set (n＝41) . The calibration curve demonstrated good agreement between predicted and observed values. Decision curve analysis (DCA) indicated that the nomogram model had good clinical utility. Conclusions The nomogram model based on β2-MG and Lp(a) has high predictive performance in assessing the risk of CSVD moderate/severe MRI burden, with good discrimination and calibration.

Objective: To analyze the serological characteristics of anti-Mur antibodies and investigate the distribution frequency of the Mur antigen among voluntary blood donors in Shiyan, thereby providing a basis for guiding clinical transfusion and establishing a Mur blood type database. Methods: ABO blood grouping of donors and patients was performed using an automated blood typing analyzer and the gel card method, respectively. Unexpected antibody screening and identification were performed using the saline, tube anti-human globulin, and polybrene methods. The specificity of anti-Mur antibodies was confirmed using Fisher's exact probability test. Plasma treated with 2-mercaptoethanol was used to distinguish IgM and IgG antibodies. IgM and IgG anti-Mur titers were determined by the saline tube method and the anti-human globulin tube method, respectively, at 4℃, room temperature, and 37℃. A total of 1 659 donor red blood cell samples were initially screened for the Mur antigen phenotype using three samples of human-derived anti-Mur plasma by the micro-tube method. Donors who tested positive for Mur antigen were further tested by the direct antiglobulin test (DAT); those with negative results were confirmed for Mur antigen by the gel card and polybrene methods. Results: Three blood samples were identified to contain mixed IgG and IgM anti-Mur antibodies. The titers of both IgM and IgG anti-Mur antibodies were highest at 4℃, intermediate at room temperature, and lowest at 37℃. The positive frequency of the Mur antigen among voluntary blood donors in Shiyan was 1.99% (33/1 659). Conclusion: anti-Mur antibodies were detected in both blood donors and patients in our region. The Mur antigen shows a certain distribution frequency among voluntary blood donors in Shiyan. Screening for the Mur blood type and establishing a corresponding database could enhance transfusion safety.

To explore the effect and mechanism of sodium propionate and mixed short-chain fatty acids on colitis induced by Citrobacter rodentium (C.r.) in mice. Mice were induced by oral gavage of C.r. The C.r. growth monitoring, histopathological analysis, qPCR analysis, intestinal permeability test and flow cytometry was used to study the effects of sodium propionate and mixed short-chain fatty acids on intestinal infection. The results showed that sodium propionate could inhibit the growth of C.r. more effectively than mixed short-chain fatty acids. Results of animal experiments showed that sodium propionate significantly reduced the weight loss and intestinal bacterial output in mice. Meanwhile, compared with mixed short chain fatty acids, sodium propionate effectively alleviated the pathological manifestations of colonic inflammatory infiltration, destruction of epithelial cell structure and decrease of goblet cell caused by C.r. infection, also increased the levels of antimicrobial peptides like interleukin-17 (IL-17) and regenerated islet derived protein 3γ (Reg3γ). In addition, sodium propionate decreased intestinal permeability better than mixed short-chain fatty acids, and sodium propionate significantly induced T helper cells 17 (Th17) and regulatory T cells (Treg) differentiation. The results showed that sodium propionate significantly alleviated colitis induced by C.r. infection compared with mixed short-chain fatty acids, which may be related to its inhibition of C.r. growth and enhancement of intestinal anti-infective function. The expected results can provide a safer and effective treatment strategy and scientific basis for colitis.

Purpose/Significance To bridge the digital service gap of the digital wellness consortium in Zhejiang province.Method/Process The study systematically reviews the evolution and development of digital elderly care theories and practices,using the digital wellness consortium in Zhejiang province as a case study,and examines it from theoretical,modeling,and practical dimensions.Result/Conclusion The digital wellness consortium has made rapid progress in recent years,however,it still faces numerous challenges in provi-ding digital elderly care services.From the perspective of digital adaptation for the elderly,the development strategies for the consortium are proposed at the government,corporate,and community levels.

Objective To investigate the clinical characteristics and genetic causes in 2 patients with hypopar-athyroidism,sensorineural deafness and renal dysplasia syndrome(HDR).Methods A retrospective analysis of au-diology,gene detection,and other clinical diagnostic data was performed on 2 patients diagnosed with HDR syn-drome.Results Patient 1 failed the newborn hearing screening(otoacoustic emission)and was diagnosed with mod-erate sensorineural hearing loss through audiology evaluation.Follow-up tests of blood calcium and parathyroid hor-mone levels were normal,and ultrasound examinations of the urinary system and parathyroid gland showed no ab-normalities.Patient 2 passed the newborn hearing screening but failed the 3-year-old physical examination(otoa-coustic emission)and was diagnosed with moderate sensorineural hearing loss.Follow-up tests of blood calcium and parathyroid hormone levels were normal,and the parathyroid gland ultrasound showed no abnormalities,but the re-nal ultrasound showed bilateral small renal calculi with normal morphology.Both patients were diagnosed with HDR syndrome through gene testing,and the 2 GAT A3 gene mutation sites(c.867dup,c.65_68dup)causing the disease were both reported for the first time.Conclusion The clinical phenotypes of HDR syndrome are highly variable.Children with suspected hearing loss accompanied by hypoparathyroidism or renal dysfunction should have gene tes-ting and other related examinations as soon as possible to avoid misdiagnosis.

Objective To construct lipid nanoparticles(lipopeptide-lipid nanoparticle,LP-LNP)with novel lipopeptides as adjuvants,and initially explore their synergistic effect on mRNA vaccines.Methods Two novel lipopeptides,SS-10 and SQ18,were designed and synthesized.Microfluidic technology was used to encapsulate lipopeptides in different proportions,as well as mRNAs encoding enhanced green fluorescent protein(eGFP),firefly luciferase(F-luc),and ovalbumin(OVA)into lipid nanoparticles to construct an mRNA delivery system with novel lipopeptides as adjuvants(LP-LNP).The particle size and polydispersity coefficient of LP-LNP were measured using dynamic light scattering.The activation effect on Toll-like receptors 2(TLR2)was detected using HEK-BlueTM mTLR2 reporter cells to screen the optimal lipopeptide ratio.The preferred LP-LNP-eGFP-mRNA was transfected into HEK293T cells,and the expression of eGFP was observed under a fluorescence microscope.In vivo imaging was used to investigate the expression level of LP-LNP-F-luc-mRNA in mice.Flow cytometry was used to evaluate the ability of LP-LNP-OVA-mRNA to induce the maturation of dendritic cells(DCs)in draining lymph nodes and cross-presentation of antigens after immunization.Results Lipopeptides SQ18 and SS-10 were incorporated into LNP at 0.50％and 0.75％molar ratios,respectively,to obtain LP-LNP with uniform particle size,high encapsulation efficiency,and good in vitro safety.The ability of this formulation to activate TLR2 was significantly stronger than the positive control Pam2CSK4(P＜0.01).The preferred LP-LNP obtained effective in vitro transfection,and LP-LNP prepared with SQ18 at 0.50％molar ratio had significantly better in vivo transfection efficiency than traditional LNP(P＜0.01),and significantly promoted the maturation of DCs in draining lymph nodes and cross-presentation of antigens(P＜0.05).Conclusion LP-LNP with novel lipopeptides as adjuvants can enhance the delivery capacity of mRNA and further improve the immune effect of mRNA vaccines.