Background: Heterozygous pathogenic variants in HNF4A gene cause maturity-onset diabetes of the young type 1 (MODY1). The mutation carriers for MODY1 have been reported to be relatively rare, in contrast to the most frequently reported forms of MODY2 and MODY3.Methods: Whole exome sequencing (WES) and Sanger sequencing were performed for genetic analysis of MODY pedigrees. Tertiary structures of the mutated proteins were predicted using PyMOL software.Results: Three heterozygous missense mutations in the HNF4A gene, I159T, W179C, and D260N, were identified in the probands of three unrelated MODY families using WES, one of which (W179C) was novel. Cascade genetic screening revealed that the mutations co-segregated with hyperglycemic phenotypes in their families. The molecular diagnosis of MODY1 has partly transformed its management in clinical practice and improved glycemic control. The proband in family A successfully converted to sulfonylureas and achieved good glycemic control. Proband B responded well to metformin combined with diet therapy because of his higher body mass index (BMI). The proband in family C, with paternal-derived mutations, had markedly defective pancreatic β-cell function due to the superposition effect of T2DM susceptibility genes from the maternal grandfather, and he is currently treated with insulin. In silico analysis using PyMOL showed that the I159T and D260N mutations altered polar interactions with the surrounding residues, and W179C resulted in a smaller side chain.Discussion: We identified three heterozygous missense mutations of HNF4A from Chinese MODY families. Structural alterations in these mutations may lead to defects in protein function, further contributing to the hyperglycemic phenotype of mutation carriers.

Objective: To ascertain whether vascular complications and high lipoprotein (a) [Lp(a)] concentrations are related in individuals with early-onset type 2 diabetes mellitus (T2DM).Methods: This observational cross-sectional study included 591 individuals with early-onset T2DM who were divided into four groups based on Lp(a) values which was measured using immunoturbidimetry and presented as mg/dL: high, >50; intermediate, 30≤Lp(a)<50; low, 10≤Lp(a)<30; and very low, 0.05). Individuals in the low Lp(a) (OR=2.12, 95% CI 1.17-3.84, P<0.05), intermediate Lp(a) (OR=2.76, 95% CI 1.10-6.98, P<0.05) and high Lp(a) (OR=4.79, 95% CI 2.03-11.31, P0.05).Conclusions: In patients with early-onset T2DM, Lp(a) concentration was independently associated with CHD. Lp(a) testing is essential to determine who has a latent high risk of CHD among patients with early-onset T2DM.

The prevalence of multidrug-resistant Klebsiella pneumoniae (K. pneumoniae) poses a severe threat to the global economy and public health, driving a resurgence of interest in phage therapy. Consequently, it is imperative to isolate lytic phages against K. pneumoniae with potent bactericidal activity. This study reports the isolation and characterization of the phage HHU1 against K. pneumoniae from hospital sewage, to evaluate its potential for phage therapy. Phage HHU1 has an icosahedral head and retractable tail, similar to members of the Jedunavirus genus. Host range tests revealed that phage HHU1 obligately lysed K. pneumoniae of the K2 serotype. Genome sequencing analysis showed that the genome of phage HHU1 was 47,779 bp in length, with a GC content of 49.2%, encoding 78 open reading frames, and lacked genes associated with lysogeny and virulence. The rapid adsorption (8 min), short latent period (10 min), and high burst size (approximately 134 PFU/cell) indicate robust replication kinetics of phage HHU1. Phage HHU1 remained stably active even after incubation for 6 h at pH 5.0-10.0 and temperature 4-40°C. In addition, phage HHU1 with different MOIs can completely inhibit the growth of drug-resistant K. pneumoniae within 8 h in vitro and significantly reduce biofilm formation of drug-resistant bacteria. Notably, treatment with high-dose phage HHU1 (MOI = 0.1 and 1) achieved 100% survival in Galleria mellonella larvae infected with drug-resistant K. pneumoniae. These findings demonstrate the potential of phage HHU1 as a promising therapeutic candidate against drug-resistant K. pneumoniae infections.

Existing studies on the association between the triglyceride-glucose index (TyG) and hypertension often rely on simplified hypertension classifications and provide limited evidence specific to the elderly population (aged ≥ 70 years). This study aims to explore the relationship between the TyG index and different subtypes of abnormal blood pressure in older adults. A cross-sectional study was conducted in 2022 using random cluster sampling, including 12,690 permanent residents aged ≥ 70 years from rural communities. Blood pressure was measured by uniformly trained staff using calibrated electronic sphygmomanometers under resting conditions. The triglyceride-glucose (TyG) index was analyzed both as a continuous variable and in quartiles. Multivariable logistic regression models, adjusted for age, sex, education level, marriage, smoking, alcohol consumption, family history of diabetes, family history of hypertension, heart rate, and body mass index, were used to assess the associations between the TyG index and hypertension subtypes. The discriminatory ability of the TyG index was evaluated using receiver operating characteristic (ROC) curve analysis, with adjustment for the same set of covariates. The overall crude prevalence of hypertension (HTN) was 55.9%. The prevalence rates of systolic hypertension (SHTN), grade 1 hypertension (HTN-I), and grade 2 hypertension (HTN-II) were 37.6%, 37.5%, and 18.3%, respectively. Participants in the highest TyG index quartile had a significantly increased risk of all hypertension subtypes compared to those in the lowest quartile. Trend analysis showed that each 1-unit increase in the TyG index was associated with increased risks of HTN (OR = 1.39, 95% CI: 1.18-1.63), SHTN (OR = 1.33, 95% CI: 1.11-1.60), HTN-I (OR = 1.30, 95% CI: 1.09-1.55), and HTN-II (OR = 1.52, 95% CI: 1.22-1.89) (P for trend < 0.01). ROC curve analysis determined optimal TyG cutoff values for predicting HTN (8.96), SHTN (8.96), HTN-I (8.96), and HTN-II (9.11), but modest discriminatory ability of the TyG index for these abnormal blood pressure subtypes (all P < 0.001), with areas under the curves (AUCs) ranging from 0.56 to 0.58. An elevated TyG index is independently associated with abnormal blood pressure in the elderly, with a particularly strong association observed for HTN-II. Although its discriminatory power as a standalone diagnostic tool is limited, the index may serve as a useful auxiliary factor for hypertension risk assessment in this population.