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 investigate the regulatory effects of LINC00467 on proliferation and metastasis of lung adenocarcinoma cells and the involvement of autophagy in its regulatory mechanism.Methods LINC00467 expression levels in lung adenocarcinoma tissues and their correlation with the patients'survival outcomes were analyzed using data from TCGA database.LINC00467 expression was also examined using qRT-PCR in human bronchial epithelial cells 16HBE and lung adenocarcinoma cell lines A549 and H1299.In A549 and H1299 cells transfected with a short hairpin RNA targeting LINC00467(shLINC00467),the effects of 3-methyladenine(3-MA,an autophagy inhibitor)and BML-275(an AMPK inhibitor)treatment on cell proliferation,migration,and expressions of LC3 and the AMPK/mTOR pathway proteins were tested using colony formation assay,wound-healing and Transwell assays,immunofluorescence staining and Western blotting.GSEA enrichment analysis was conducted to analyze the correlation between LINC00467 and the autophagy pathway.Results The expression level of LINC00467 was significantly higher in lung adenocarcinoma tissues than in the adjacent tissues(P<0.001)and increased progressively with the clinical stage(P<0.05),and its high expression was associated with a poor overall survival(P=0.049)and a high first progression rate(P=0.026)of the patients.LINC00467 expression was also significantly higher in A549 and H1299 cells than in 16HBE cells.In A549 and H1299 cells,LINC00467 knockdown significantly decreased colony-forming,migration and invasion abilities of the cells,lowered p-mTOR/mTOR and p62 expressions,and increased p-AMPK/AMPK expressions and LC3Ⅱ/Ⅰ ratio,and these effects were strongly attenuated by application of either 3-MA or BML-275.GSEA analysis suggested an inhibitory effect on LINC00467 on the autophagy pathway(|NES|>1,P<0.05,FDR<0.25).Conclusion High expressions of LINC00467 promote proliferation and metastasis of lung adenocarcinoma cells possibly by inhibiting cell autophagy mediated by the AMPK/mTOR signaling pathway.

Objective:To determine the incidence of adrenal incidentalomas(AIs) in patients with diabetes mellitus and the metabolism profiles.Methods:A total of 615 hospitalized patients with diabetes mellitus in the Department of Endocrinology and Metabolism of Peking University People′s Hospital from March 2020 to May 2021 were retrospectively included in this study. AIs were screened by unenhanced chest computed tomography(CT) retrospectively and subsequently confirmed by multiplanar reconstruction. Participants′ physical indicators, metabolic profiles, and adrenal function parameters were collected. Unpaired t test, Mann-Whitney U test, and Chi-Square test were adopted to compare the metabolism profiles between diabetes mellitus patients with or without AIs. Regression models were used to estimate the correlations between AIs and the metabolism profiles such as blood glucose, blood lipids, blood pressure, and the adrenal function parameters.Results:Twenty-seven out of 615 participants were detected with AIs(4.4%). Patients with AIs had higher body mass index, waist circumference, and hip circumference than patients without AIs [(29.4±5.1)kg/m 2vs(26.8±3.8)kg/m 2,P=0.018; (102.3±11.7)cm vs(95.8±10.3)cm, P=0.002; (107.3±10.1)cm vs(101.4±7.6)cm, P=0.008]. The levels of serum uric acid and urinary albumin/creatinine ratio were also significantly increased in patients with AIs [(409.6±118.1)μmol/L vs(357.4±100.6)μmol/L, P=0.009; 21.25(7.49, 180.24)mg/g vs 8.60(4.71, 34.56)mg/g, P=0.010]. Besides, individuals with AIs were also associated with a higher risk of co-existing hypertension( P=0.045). Conclusion:The incidence of AIs in patients with diabetes is 4.4%. The presence of AIs in patients with diabetes may associated with increased risk of obesity and hypertension.

Objective:To explore the impact of digital technology in constructing a three-dimensional (3D) symmetry reference plane (SRP) for esthetic restoration of anterior teeth and to evaluate its clinical applicability.Methods:A cross-sectional study was conducted from February to May 2024, involving 20 patients [11 males and 9 females, aged (36.8±11.4) years] who underwent anterior esthetic restorations at the Department of Stomatology, People′s Hospital of Ningxia Hui Autonomous Region. Symmetrical reference planes of patients′ 3D facial models were constructed using three different algorithms: weighted Procrustes analysis (WPA), Procrustes analysis (PA) based on the ontology-mirror correlation method, and iterative closest point (ICP). The SRP defined by an associate chief physician served as the control (true-value group). The angular errors between each algorithm group and the true-value group were compared. The optimal algorithm was selected and combined with a three-dimensional digital smile design (DSD) to create virtual patients, followed by designing anterior restorations. The visual analogue scale (VAS) was used by patients to score the aesthetic restoration results of the conventional design (control group) and the algorithm-based design (algorithm group).Results:The angular errors of the WPA, PA, and ICP groups were 1.43°±0.66°, 1.82°±0.88°, and 4.74°±2.03° respectively, with statistically significant differences among the groups ( F=41.10, P<0.001). Pairwise comparisons showed that the WPA group had significantly smaller angular errors compared to the PA and ICP groups ( P<0.05). The VAS scores for aesthetic restoration were significantly higher in the algorithm group (8.09±0.74) compared to the control group (6.30±1.38) ( t=-5.49, P<0.001). Conclusions:The SRP constructed using the WPA algorithm demonstrated minimal angular error when compared to the expert-defined SRP and is considered the optimal choice in clinical practice, yielding high patient satisfaction.

Objective To investigate the regulatory effects of LINC00467 on proliferation and metastasis of lung adenocarcinoma cells and the involvement of autophagy in its regulatory mechanism.Methods LINC00467 expression levels in lung adenocarcinoma tissues and their correlation with the patients'survival outcomes were analyzed using data from TCGA database.LINC00467 expression was also examined using qRT-PCR in human bronchial epithelial cells 16HBE and lung adenocarcinoma cell lines A549 and H1299.In A549 and H1299 cells transfected with a short hairpin RNA targeting LINC00467(shLINC00467),the effects of 3-methyladenine(3-MA,an autophagy inhibitor)and BML-275(an AMPK inhibitor)treatment on cell proliferation,migration,and expressions of LC3 and the AMPK/mTOR pathway proteins were tested using colony formation assay,wound-healing and Transwell assays,immunofluorescence staining and Western blotting.GSEA enrichment analysis was conducted to analyze the correlation between LINC00467 and the autophagy pathway.Results The expression level of LINC00467 was significantly higher in lung adenocarcinoma tissues than in the adjacent tissues(P<0.001)and increased progressively with the clinical stage(P<0.05),and its high expression was associated with a poor overall survival(P=0.049)and a high first progression rate(P=0.026)of the patients.LINC00467 expression was also significantly higher in A549 and H1299 cells than in 16HBE cells.In A549 and H1299 cells,LINC00467 knockdown significantly decreased colony-forming,migration and invasion abilities of the cells,lowered p-mTOR/mTOR and p62 expressions,and increased p-AMPK/AMPK expressions and LC3Ⅱ/Ⅰ ratio,and these effects were strongly attenuated by application of either 3-MA or BML-275.GSEA analysis suggested an inhibitory effect on LINC00467 on the autophagy pathway(|NES|>1,P<0.05,FDR<0.25).Conclusion High expressions of LINC00467 promote proliferation and metastasis of lung adenocarcinoma cells possibly by inhibiting cell autophagy mediated by the AMPK/mTOR signaling pathway.

AIM: To explore the effect of knocking down long intergenic non-coding RNA 00467 on the prognosis of patients with lung adenocarcinoma and its mechanism. METHODS: Quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression level of linc00467 in the plasma of LAD patients and healthy volunteers. The overall survival (OS) was analyzed by Kaplan-Meier survival analysis and log-rank tests. Cell proliferation assays and Xenograft mouse model were used to confirm the effect of linc00467 expression on tumorigenesis in vitro and in vivo.RESULTS: linc00467 expression was up-regulated in the plasma of LAD patients compared with healthy volunteers. In addition, high levels of linc00467 expression were correlated with larger tumour sizes, lymph node metastasis and advanced TNM stages. High levels of linc00467 indicated a poor prognosis in LAD patients, multivariate analyses indicated that linc00467 expression could serve as an independent prognostic factor for overall survival of LAD. Functional experiments showed that knockdown of linc00467 could inhibit LAD cell proliferation in vitro and in vivo. CONCLUSION: linc00467 is involved in the progression of LAD and that linc00467 may be a novel diagnosis biomarker and a potential therapeutic target for LAD.

Objective To evaluate the safety and feasibility of reconstruction technique of atrial septum puncture trajectory with the help of three - dimensional mapping system in performing radiofrequency catheter ablation for atrial fibrillation. Methods Sixty- eight consecutive patients with atrial fibrillation received two times of atrial septum puncture under fluoroscopic guidance to perform radiofrequency catheter ablation. Carto 3, a three - dimensional mapping system, was employed to construct the real time left atrium and pulmonary vein anatomy by using a rapid anatomical mapping (FAM) model. Then, FAM model was used to construct the trajectory, along which the ablation catheter passed from left atrium through the long sheath to the right atrium and finally into the inferior vena cava. The safety and the feasibility of this catheter trajectory, which could allow the catheter repeatedly enter the left atrium, were evaluated. Results By using 3D-reconstruction technique of atrial septum puncture trajectory, the ablation catheter could repeatedly enter the left atrium at right anterior oblique position as well as at left anterior oblique position under zero X-ray fluoroscopy. The average time spent for the procedure was (12. 18±2. 28) seconds. No any complication occurred. Conclusion The reconstruction technique of atrial septum puncture trajectory with the help of three-dimensional mapping system is simple and feasible, the ablation catheter can repeatedly enter the left atrium, the X-ray exposure time spent for catheter ablation of atrial fibrillation can be greatly reduced. (J Intervent Radiol, 2018, 27: 204-206)