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 establish a mouse model of bronchiectasis with acute infection and evaluate the immunogenicity and protective effect of a self-assembling Pseudomonas aeruginosa(PA)nanoparticle vaccine rePO-FN based on fusion of PcrV-OprI(rePO)protein with self-assembling ferritin(Ferritin).Methods ① SPF-grade female C57BL/6 mice(aged 6～8 weeks,weighing 18～20 g)were randomly allocated into normal saline group,and low-,medium-and high-dose elastase groups(n=6).A mouse model of bronchiectasis was established via intratracheal instillation of different doses of elastase(30 μL of normal saline containing 0.65,1.30 and 2.60 IU elastase)for 3 consecutive days.At 14 and 21 d after modeling,ELISA and HE staining were performed respectively to detect the concentration of IL-6 and to observe pathological changes in lung tissue in order to confirm the modeling.② A recombinant plasmid encoding the gene of fusion protein rePO-FN was constructed and expressed in E.coli.The target protein was purified via affinity chromatography and renatured to obtain the desired protein.The physicochemical properties of the rePO-FN protein were characterized using SDS-PAGE protein gel electrophoresis,dynamic light scattering,molecular sieve chromatography,and transmission electron microscopy.③ C57BL/6J mice were randomly divided into PBS group,rePO group,rePO-FN group,and Ferritin group(n=10).The mice in the above groups were immunized intramuscularly with 100 μL PBS buffer alone or containing 10 μg of corresponding proteins on days 0,7,and 14.ELISA was used to measure the specific antibodies in serum.In 7 d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the PBS,rePO,and rePO-FN groups.After establishing a bronchiectasis model by intratracheal instillation of 2.60 IU of elastase in C57BL/6J mice as described above,the mice were randomly divided into bronchiectasis PBS group,bronchiectasis rePO group,and bronchiectasis rePO-FN group(n=10).Immunization was conducted at the same dose and procedure as described above,in 21 d after bronchiectasis modeling.At the 7th d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the groups.Results ①Repeated intratracheal instillation of elastase significantly increased the concentration of IL-6 in the lung tissue when compared to the content of the normal saline group(P＜0.05).Pathological observations revealed varying degrees of bronchial wall destruction,alveolar fusion,edema,neutrophil infiltration,and hemorrhage,with the severity increasing with elastase dose,which confirming successful establishment of the mouse model of bronchiectasis.② Well-dispersed rePO-FN nanoparticles were successfully prepared,with an average particle size of 91.28 nm,a Zeta potential of approximately-6.5 mV,and a polydispersity index(PDI)of 0.306.Molecular sieve chromatography determined the elution volume of rePO-FN protein to be 8.80 mL,corresponding to a molecular weight of approximately 1 400 kDa.③ Under acute PA XN-1 strain infection,the survival rate of the rePO-FN immunization group and the bronchiectasis rePO-FN immunization group were significantly higher than that of the PBS control group(P＜0.05).Additionally,bacterial colonization in the lung tissues was significantly lower in the rePO-FN immune group and the bronchiectasis rePO-FN immune group under acute PA XN-1 strain infection than that in the rePO group and the bronchiectasis rePO group(P＜0.05).Conclusion Our vaccine rePO-FN can effectively trigger a strong humoral immune response and provide significant protection against PA infection in a mouse bronchiectasis model.

The occurrence and development of type 2 diabetes mellitus(T2DM)are closely as-sociated with defects in insulin secretion.Synaptosomal-associated protein 25(SNAP25),as a core component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor(SNARE)complex,directly mediates the fusion of insulin secretion granules with the cell membrane and regu-lates the dynamic balance of insulin secretion stimulated by glucose.The expression defect of SNAP25 in patients with T2DM and model animals directly leads to vesicle fusion disorder,constituting the core pathological link of insulin secretion disorder and exacerbating the deterioration of β-cell func-tion.SNAP25 may serve as a key hub for multi-target synergistic intervention,and its genetic poly-morphism and the plasticity of its regulatory network offer novel strategies for precision therapy.This article innovatively integrated multidimensional regulatory mechanisms,including calcium channel ac-tivity,G-protein-coupled signaling and epigenetic modifications,to systematically analyze the spatio-temporal-specific regulatory network of SNAP25 in insulin secretion,providing a theoretical basis for T2DM therapeutic strategies targeting vesicle fusion.

Objective To study the serotype, drug resistance, and molecular typing characteristics of Salmonella enteritidis strains isolated from patients with diarrhea in Xiangyang City. Methods Serotyping, drug sensitivity test, pulsed field gel electrophoresis (PFGE) typing, and whole genome sequencing were carried out on Salmonella enteritidis strains isolated from diarrhea patients from 2019 to 2020. Results From the drug susceptibility test , Salmonella enteritidis in this region showed varying degrees of drug resistance, with 94.7% of Salmonella enteritidis strains being multidrug-resistant. The PFGE electrophoretogram of Salmonella enteritidis showed that 19 strains could be divided into 6 PFGE types by cluster analysis, among which 12 strains belonged to the epidemic dominant type. MLST typing showed that all 15 strains were ST11 type, carrying multiple drug resistance genes (mdsA, mdsB, mdsC, gols, and sdiA) and mdtK gene, and all carried various invasiveness-related virulence genes. However, there were slight differences in virulence genes related to the secretion system of the pathogenic island among the different strains. The phylogenetic tree analysis of the system evolution showed that 15 strains could be divided into 2 different evolutionary branches. Conclusion The situation of multidrug resistance in Salmonella enteritidis in Xiangyang is serious, with dominant PFGE types and ST types, and it carries multiple drug resistance genes and various invasiveness-related virulence genes.

Obstructive sleep apnea (OSA) is a common sleep disordered breathing disorder. As a major global public health problem, untreated OSA can lead to a variety of adverse health outcomes, including various cardiovascular and cerebrovascular diseases, metabolic disorders, and psychiatric disorders such as anxiety and depression. Traditional OSA therapies such as positive airway pressure (PAP), weight loss, oral appliance, upper airway surgery, and postural therapy focus on the anatomical factors of OSA. However, the pathogenesis of OSA is heterogeneous, and non-anatomical factors also play an important role in most patients. Although there is no drug with exact efficacy for the treatment of OSA, with the deepening understanding of the pathophysiological mechanism of OSA, more and more clinical studies are devoted to the study of drug treatment of OSA and its complications, and a series of results have been achieved. The following is a review of the relevant studies on drug treatment of OSA in recent years, hoping to provide literature support and theoretical basis for future research on drug treatment of OSA.

Mesenchymal stem cells(MSCs)are self-regenerating,rapidly proliferating pluripotent stem cells that depend primarily on their derived pro-angiogenic,inflammatory regulatory,and tro-phic factors to exert beneficial effects that attenu-ate deleterious inflammatory responses,reduce vascular damage,and promote tissue repair and re-generation.Obstructive sleep apnea hypoventila-tion syndrome(OSAHS)is a chronic disorder marked by oropharyngeal collapse during sleep,re-sulting in transient reduced airflow,large fluctua-tions in intrathoracic pressure,and intermittent hy-poxia and hypercapnia.OSAHS subsequently cyto-kine-mediated inflammatory cascades,oxidative stress,and ischemia,recruit MSCs from inflamed and damaged tissues through MSCs-derived of anti-inflammatory and pro-angiogenic factor activity,re-duce hypoxia,suppress inflammation,promote re-generation,and prevent fibrosis in OSAHS-injured tissues.In this paper,we will describe the patho-genesis of inflammation,oxidative stress,fibrosis and ischemia from the perspective of OSAHS,high-lighting the current research progress on MSCs-de-pendent regulation of OSAHS-related pathology.

Objective:To investigate the impact of body mass index (BMI) on the postoperative complications of open pancreaticoduodenectomy (OPD).Methods:The preoperative, operative and postoperative data of 234 patients who underwent OPD in the Department of the Hepatobiliary and Pancreatic Surgery of First Affiliated Hospital affiliated to Naval Medical University from January 2015 to June 2016 were analyzed retrospectively. According to the Asian BMI standard, the patients were divided into three groups: underweight group (BMI<18.5 kg/m 2, n=32), normal weight group (18.5 kg/m 2≤BMI<23.0 kg/m 2, n=110) and overweight group (BMI≥23.0 kg/m 2, n=92). Normal weight group was compared with underweight group and overweight group, respectively, to analyze the relationship between BMI and intraoperative parameters and major postoperative complications of OPD. Results:The incidence of diabetes in underweight group was lower than that in normal weight group, and the proportion of ASA score 3 in underweight group was higher than that in normal weight group, and there were significantly statistical differences (both P value <0.05). There was no significant difference on the other variables between underweight group, normal weight group and overweight group. The operation time, intraoperative hemorrhage volume >800 ml and intraoperative blood transfusion rate were not statistically different between underweight group and normal weight group, but overweight group had obviously higher intraoperative blood transfusion rate than normal weight group and the difference was statistically significant ( P<0.05). Underweight group had more postoperative intraperitoneal hemorrhage and postoperative blood transfusion rate than normal weight group, and the readmission rate in underweight group was less than that in normal weight group; the incidence of clinically related-post operative pancreatic fistula, postoperative infection, gastrointestinal bleeding and delayed gastric emptying in overweight group were significantly higher than those in normal weight group, and there were significantly statistical differences (all P value <0.05). In underweight group, normal weight group and overweight group, the average length of hospital stay were 9.9 days, 11.3 days, 15 days, and the total hospitalization expenses were 63663.04 yuan, 66241.78 yuan and 80484.31 yuan, respectively. Conclusions:Compared to normal weight patients, the difficulty of OPD in underweight patients does not increase, while the difficulty of OPD in overweight patients increases. Underweight and overweight could both increase the postoperative complications of OPD to some extent.