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.

17q12 deletion syndrome is a rare autosomal dominant disorder affecting multiple organ systems caused by the deletion of DNA fragments approximately 1.4～1.8 Mb in band 2 of region 1,the long arm of chromosome 17,including hepatocyte nuclear factor 1B.The clinical manifestation of the disease ismaturity-onset diabetes of youth type 5,abnormalities in renalstructure or function,as well as in neurodevelopment or psychiatric systems.

Background: in vitro culture of preantral follicles is a promising technology for fertility preservation. Objectives: This study aims to investigate an optimized three-dimensional (3D) fetal bovine serum (FBS)-free preantral follicle culture system having a simple and easy operation. Methods: The isolated follicles from mouse ovaries were randomly divided in an ultra-low attachment 96-well plates supplement with FBS or bovine serum albumin (BSA) culture or encapsulated with an alginate supplement with FBS or BSA culture. Meanwhile, estradiol (E 2 ) concentration was assessed through enzyme-linked immunosorbent assay of culture supernatants. The diameter of follicular growth was measured, and the lumen of the follicle was photographed. Spindle microtubules of oocytes were detected via immunofluorescence.The ability of oocytes to fertilize was assessed using in vitro fertilization. Results: The diameters were larger for the growing secondary follicles cultured in ultra-low attachment 96-well plates than in the alginate gel on days 6, 8, and 10 (p < 0.05). Meanwhile, the E 2 concentration in the BSA-supplemented medium was significantly higher in the alginate gel than in the other three groups on days 6 and 8 (p < 0.05), and the oocytes in the FBS-free system could complete meiosis and fertilization in vitro. Conclusions The present study furnishes insights into the mature oocytes obtained from the 3D culture of the preantral follicle by using ultra-low attachment 96-well plate with an FBSfree system in vitro and supports the clinical practices to achieve competent, mature oocytes for in vitro fertilization.

Humans ; Consensus ; Pancreatic Neoplasms/therapy* ; Neuroendocrine Tumors/therapy*

OBJECTIVE:To discuss the drug resistance situation and influential factors of sputum culture positive tuberculosis patients in a specialized subject hospital. METHODS:The information of sputum culture positive tuberculosis inpatients were col-lected from Heze infectious disease hospital during Jan. 1st 2014 to Apr. 30th 2015;the results of drug sensitive test were analyzed retrospectively by using absolute concentration method. RESULTS:Among 259 patients,137 cases were drug-resistant(52.90%), among including 69(26.64%) mono-drug resistant cases,52(20.08%) poly-drug resistant cases,15(5.79%)multi-drug resistant cases and 1(0.39%)extensively drug resistant case;streptomycin (31.66%) and amikacin (15.44%) were drugs with the highest drug-resistant rate;there was no statistical significance in resistant rate between different genders and ages(P>0.05),the rate of drug resistance in first-treatment patients was 47.21%,and that of the re-treatment patients was 70.97%,the difference was statisti-cal significant(P<0.05). In addition to ethambutol and kanamycin,other all had mono-drug resistance,there were 27 combinations of poly-drug resistance and 9 combinations of multi-drug resistance. Logistic regression analysis showed that treatment history was a risk factor for drug-resistance,the risk of re-treatment patient was 2.734 times of first-treatment patients. CONCLUSIONS:Sputum culture positive tuberculosis inpatients patients have high drug resistance and complex spectrum in the hospital;we should pay great attention to the risk of drug resistance in senile patients and re-treatment patients,and rational use of streptomycin,amikacin,isoni-azid and capreomycin.

Objective To observe the clinical characteristics of gestational diabetic retinopathy (DR)of 13 pregnants with vitreous hemorrhage.Methods The clinical data of 26 eyes retinopathy with 13 cases of gestational diabetes were retrospectively analyzed.After bilateral eyes were mydriatic by Pyrazole MAO amine compound,ophthal-mologist used fundus camera to check bilateral fundus.B ultrasonic was used to examine vitreous hemorrhage and the surfaces of vitreous and retinal.Results In 13 cases,26 eyes vision were between hand motion-0.6.Sudden vitre-ous hemorrhage in 13 eyes,accounted for 50.0%(13/26).Among them,the classⅠvitreous hemorrhage in 10 eyes, 76.9%(10/13).Ⅱ,Ⅲ grade vitreous hemorrhage in 2 eyes,15.4%(2/13).LevelⅣvitreous hemorrhage in 1 eye, accounted for 7.7%(1/13).26 eyes were diagnosed with stage IV(early or fiber hyperplasia period)DR.The fundus photography:the size,number of retinal neovascularization were found in 13 eyes without vitreous hemorrhage.Ultra-sound confirmed that the 13 eyes vitreous hemorrhage were fresh bleeding,and found 4 eyes with fiber membrane, accounted for 30.8%(4/13).The eyes without vitreous hemorrhage were timely treated by laser,and the eyes with vitreous hemorrhage were treated by stage laser treatment according to the condition of vitreous hemorrhage absorp-tion.Followed up for 4 to 6 months,in a stable condition.Conclusion Obstetrics and gynecology doctors and oph-thalmologists should pay attention to pregnancy DR with vitreous hemorrhage.Because they are all early or fiber hyper-plasia period.Timely and reasonable laser treatment can prevent permanent damage of visual function.

Objective To explore the relationship between umbilical cord blood brain-derived neurotrophic factor (BDNF) and neonatal neurobehavioral development in lead exposure infants. Methods All infants and their mother were randomly selected during 2011 to 2012, subjects were selected according to the umbilical cord blood lead concentrations, which contcentration of lead was higher than 0.48μmol/L were taken into high lead exposure group, about 60 subjects included. Comparing to the high lead exposure group, according to gender, weight, pregnant week, length and head circumferenece, the level of cord blood lead concentration under 0.48μmol/L were taken into control group, 60 cases included. Lead content was determined by graphite furnace atomic absorption spectrometry. Neonatal behavioral neurological assessment (NBNA) was used to determine the development of neonatal neuronal behavior. The content of BDNF was detected by ELISA. Comparing the BDNF and the NBNA score between two groups, and linear correlation was given on analysis the correlation between lead concentration in cord blood and BDNF, BDNF and the NBNA score. Results Lead content in high exposure group was(0.613± 0.139)μmol/L,and higher than(0.336±0.142)μmol/L in low exposure group(t=3.21,P<0.001). NBNA summary score (36.35±1.86), active muscle tension score (6.90±0.27) and general assessment score (5.93± 0.32) in high exposure group were lower than those(38.13 ± 0.96, 7.79 ± 0.35, 6.00 ± 0.00)in low exposure group(t values were 8.21, 10.23, 2.32,respectively,P values were <0.001,<0.001 and 0.037). BDNF content in high exposure group which was(3.538±1.203)ng/ml was higher than low exposure group(2.464± 0.918)ng/ml (t=7.60,P<0.001). The correlation analysis found that the cord blood BDNF content was negatively correlated with NBNA summary score, passive muscle tension and active muscle tone score(r was-0. 27,-0.29,-0.30, respectively ,P values were <0.001, respectively). Conclusion Prenatal lead exposure results poor neonatal neurobehavioral development and cord blood BDNF was negatively correlated with neonatal neurodevelopment, may serve as a useful biomarker.