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 explore the medical reference values, distribution characteristics and influencing factors of serum iodine in adults with different thyroid health conditions, and to evaluate the importance of serum iodine in evaluating individual iodine nutrition.Methods:From February 2017 to November 2018, multi-stage stratified cluster sampling was used to select one community and one agricultural (fishing) village in the coastal Yingkou City and the inland areas of Shenyang City of Liaoning Province as survey sites. Cluster sampling of adults over 18 years old who had lived for five years were conducted with questionnaire survey, clinical physical examination and thyroid ultrasound examination. Fasting venous blood samples and one random urine sample were collected from all subjects for serum iodine, thyroid hormone, antibody and urine iodine detection. The 95% medical reference value of serum iodine was established by using the percentage quantile method, and the reference value, distribution characteristics and influencing factors of serum iodine in adults with different thyroid health status were analyzed. The diagnostic value of iodine nutritional indicators in thyroid diseases was evaluated by the receiver operating characteristic (ROC) curve.Results:A total of 2 931 adults were surveyed, with serum iodine levels of 62.1 (53.6, 72.2) μg/L, ranging from 5.6 to 642.3 μg/L; urine iodine was 167.6 (111.2, 244.2) μg/L, and the overall iodine level was at an appropriate level. A total of 1 089 patients with thyroid diseases were examined, with a detection rate of 37.2% (1 089/2 931); among them, there were 597 cases of thyroid nodules, 56 cases of endemic goiter, 42 cases of hypothyroidism, 161 cases of subclinical hypothyroidism, 27 cases of hyperthyroidism, 18 cases of subclinical hyperthyroidism, and 474 cases of autoimmune thyroid disease (AITD). There was a statistically significant difference in the detection of thyroid diseases among adults with different levels of serum iodine (χ 2 = 13.80, P < 0.05). The reference values of serum iodine in normal adults, hypothyroidism (without thyroid hormone intervention), hyperthyroidism (without anti thyroid hormone drug treatment), AITD, endemic goiter, and thyroid nodules were 37.2 - 103.0, 12.5 - 52.8, 49.9 - 163.1, 34.3 - 129.3, 27.3 - 92.8, and 37.9 - 119.5 μg/L, respectively. The ROC curve analysis results showed that the serum iodine area under curve(AUC) of patients with hyperthyroidism, subclinical hyperthyroidism, endemic goiter, thyroid nodules, and AITD were 0.94, 0.61, 0.55, 0.53, and 0.52, respectively. The results of univariate analysis showed that there were statistically significant differences in adult serum iodine levels among different positions, regions, age, education level, occupation, iodine intake, blood pressure, and body mass index ( P < 0.05). Conclusions:There are significant differences in serum iodine levels among adults with different thyroid health conditions, and evaluation standards and systems should be developed separately. Serum iodine is an important indicator for evaluating individual iodine nutrition.

Objective:To explore the associations of urinary retinol binding protein (RBP) and β 2-microglobulin (β 2-MG) with urinary albumin to creatinine ratio (UACR) and renal function in hospitalized patients with type 2 diabetes mellitus (T2DM). Methods:A total of 1 030 Chinese patients with T2DM were included in this study. The subjects were divided into the UACR normal group (<30 mg/g), microalbuminuria group (30-300 mg/g) and macroalbuminuria group (>300 mg/g). Patients with normal UACR were further divided into two groups according to the estimated glomerular filtration rate (eGFR): the eGFR low group (<90 ml·min -1·1.73m -2) and the normal eGFR group (≥90 ml·min -1·1.73m -2). Urine RBP and β 2-MG levels among the groups were compared. Multiple linear regression analyses were applied to evaluate risk factors of urine RBP and β 2-MG. Results:In all patients ( n=1 030), urine RBP and β 2-MG increased gradually with the increase of UACR across the three groups, the proportions of abnormal urine RBP (>0.7 mg/L) and β 2-MG (>370 μg/L) in these groups were 3.8%, 8.5%, 39.0% ( P<0.001), and 12.9%, 26.7%, 46.8% ( P<0.001), respectively. In the UACR normal group ( n=788), 12.2% of the patients were with eGFR<90 ml·min -1·1.73m -2. The proportion of abnormal β 2-MG (>370 μg/L) was higher in the eGFR low group than that in the eGFR normal group (29.2% vs. 10.7%, P<0.001). Multivariate linear stepwise regression analyses were performed using natural logarithm of urine RBP or β 2-MG as dependent variable, and showed that urine RBP was independently associated with UACR ( β=0.0005, P<0.001), serum creatinine ( β=0.006, P<0.001) and glycosylated hemoglobin A1c ( β=0.050, P=0.001), and β 2-MG was independently correlated with UACR ( β=0.000 4, P<0.001), serum creatinine ( β=0.011, P<0.001), systolic blood pressure ( β=0.005, P=0.031) and fasting blood-glucose ( β=0.027, P=0.046). Conclusions:Urine RBP and β 2-MG are positively associated with high UACR and impaired renal function in T2DM patients, and these changes could occur before UACR and eGFR turned out to be abnormal. It is recommended that urine RBP and β 2-MG be detected as early as possible to identify diabetic kidney disease in patients with normal UACR and eGFR.

Objective To analyze the iodine nutritional status of children and pregnant women in Liaoning Province,and the iodine content of edible salt suitable for iodine nutrition level,to provide a basis for adjusting the suitable salt iodine content standard of key population.Methods In 2015-2018,a cross-sectional survey method was used to conduct iodine nutritional status surveys in counties (districts) within the jurisdiction of Liaoning Province.One township (community) was selected in each county (district)according to the east,west,south,north,and middle directions.Forty children aged 8-10 (age and gender distribution balanced) and 20 pregnant women were selected in each township (community),urine and household salt samples were collected from children and pregnant women,to test urine and salt iodine levels;and the water samples from all township (community) water supply plants in the province were collected for water iodine detection in 2017;and all respondents were calculated the dietary iodine intake.The multi-order linear curve was used to fit the salt iodine content suitable for children and pregnant women.Results A total of 1 549 townships (communities) were surveyed,including 1 125 centralized water supply townships (communities) with water iodine ＜ 40 μg/L;50 820 children aged 8-10 and 26 707 pregnant women were selected from the centralized water supply towns.The average iodine content of edible salt was 24.0 and 23.9 mg/kg,respectively.The median urinary iodine level of children was 168.5 μg/L,at the appropriate level of iodine;the median urinary iodine level of pregnant women was 137.8 μg/L,at the deficiency level of iodine.The average dietary intake of iodine in children was 228.4 μg/d,which was 3.51 times of the standard iodine requirement (EAR,65 μg/d) and 2.54 times of the recommended intake (RNI,90 μ g/d).The average dietary intake of iodine in pregnant women was 273.4 μg/d,which was 1.71 times of the EAR (160 μg/d) and 1.19 times of the RNI (230 μg/d),and 21.4％ (5 728/26 707) of pregnant women had lower iodine intake than RNI,the iodine intake was insufficient.After multi-level linear curve fitting combined with monitoring data,the iodine content range of edible salt in children's urine was suitable and the iodine intake in RNI-tolerable intake (UL,300 μg/d) was 13-25 mg/kg (20 mg/kg + 20％);the iodine content range of edible salt in pregnant women's urinary iodine was suitable and the iodine intake in RNI-UL (600 μg/d) is 25-37 mg/kg (31 mg/kg + 20％).Conclusions Under the current salt iodine content standard (25 mg/kg) in Liaoning Province,children's iodine nutrition is generally at the level of iodine appropriate;pregnant women's iodine nutrition is generally at the level of iodine deficiency.It is recommended that all regions should revise the iodine content standard for edible salt in due course in combination with the iodine nutritional status of key populations within the jurisdiction.

Objective To study the status of prevention and control of iodine deficiency disorders (IDD),master the iodine nutritional status of children and pregnant women in Liaoning Province.Methods One hundred counties (districts) of Liaoning Province,34 counties (districts) were randomly selected to carry out a cross-sectional survey on iodine nutritional status of the population according to "National Surveillance Program on IDD" in 2016.Five townships (communities) were randomly selected according to their sub-area positions of east,west,south,north and center,1 primary school was randomly selected in each township (communities),40 non boarding students aged 8-10 (half males half females) were selected from each school.The radial size of the thyroid was measured by Ultra-portable Doppler Diagnostic Ultrasound System and the volume was calculated.Twenty pregnant women were randomly selected in each township (communities).Their salt and random urine samples were collected;salt iodine level and urinary iodine level were tested.Results The mean of salt iodine content of 6 874 children's family salt samples was (24.0 ± 4.7) mg/kg,the iodized salt coverage rate was 98.4％ (6 761/6 874) and the consumption rate of qualified iodized salt was 95.5％ (6 567/6 874).The median urinary iodine (MUI) of 6 874 children's urine samples was 168.0 μg/L,and children's goiter rate was 1.6％ (111/6 874).The mean of salt iodine content of 3 404 pregnant women's family salt samples was (24.1 ± 4.3) mg/kg,the iodized salt coverage rate was 99.0％ (3 369/3 404) and the consumption rate of qualified iodized salt was 84.6％ (2 880/3 404).The MUI 3 404 of pregnant women's urine samples was 135.8 μg/L (＜ 150 μg/L).Conclusions In 2016,8-10 years old children's urinary iodine is at adequate level.But the pregnant women are in iodine deficiency.

Objective To master the disease trend of Keshan disease in Liaoning Province, and provide a scientific basis for control and elimination of Keshan disease. Methods Retrospective method was used to analysis the Keshan disease monitoring in Liaoning Province.From 1995 to 2007,a sentinel surveillance method was used in Qingyuan County,and seriously ill villages were selected as monitoring sites. From 2008 to 2014, a sample random sampling method was adopted to randomly select 1 - 4 diseased villages as monitoring sites in Qingyuan, Xinbin, Huanren and Xifeng each year. The residents in surveillance sites were surveyed through questionnaire, clinically examined and did electrocardiogram (ECG), suspected cases were taken anterior chest X-rays in the distance of 2 meters, and diagnosis of Keshan disease was based on the "Standard of Diagnosis of Keshan Disease" (GB 17021-1997)and the"Keshan Disease Diagnosis" (WS/T 210-2011). Results From 1995-2014,no new cases of acute and subacute Keshan disease were detected in Keshan disease monitoring sites in Liaoning Province,Keshan disease detection rate was the highest in 2007(6.6%,55/838),the lowest was in 2012(0.4%,3/836),cases of Keshan disease had been concentrated among non-key groups,the highest abnormal rate of ECG was found in 2011 (24.5%,424/1 728), for 176 cases of suspected Keshan disease, the anterior position of 2 m chest X-ray was taken and 50.0% (88/176) of the changes were increased. Conclusion After 20 years of monitoring and prevention, the condition of Keshan disease in Liaoning Province has been in a relatively stable state. But we still should strengthen the monitoring of Keshan disease,emphasize the importance of case search,continue to carry out the monitoring.

Objective To investigate the clinical efficiency,safety and prognostic factors of secondline chemotherapy regimen with gemcitabine combined with rituximab in the treatment of relapsed or refractory B-cell non-Hodgkin lymphoma.Methods A total of 157 patients with relapsed or refractory B-cell nonHodgkin lymphoma were selected from July 2008 to February 2015 in Xi'an Central Hospital.Among them,87 patients were given GEMOX regimen (gemcitabine + oxaliplatin) combined with rituximab,and 70 patients were given GDP program (gemcitabine + cisplatin + dexamethasone) combined with rituximab.The chemotherapy efficacies of the two groups were evaluated.At the same time,the patients were grouped according to whether rituximab was applied or not,and the total objective response rate (ORR) difference was compared.The relevant prognostic factors affecting overall survival (OS) were found.The adverse reactions of patients after treatment were observed.Results The ORR of the GEMOX regimen combined with rituximab group was 65.5％,and the ORR of the GDP regimen combined with rituximab group was 55.7％,but the difference between the two groups was not statistically significant (x2 =1.58,P =0.210).The ORR was 75.2％ in 105 patients who had not used rituximab,and the ORR was 32.7％ in 52 patients who had previously received rituximab.The difference between the two groups was statistically significant (x2 =29.50,P ＜ 0.001).Univariate analysis showed that middle-high risk or high risk of the lymphoma international prognostic index (IPI) score (x2 =69.21,P ＜0.001),lactate dehydrogenase (LDH) increased (x2 =16.90,P ＜0.001),refractory patients (x2 =14.43,P =0.001),large mass (x2 =4.57,P =0.030),and failure to achieve CR or PR after salvage chemotherapy (x2 =50.85,P ＜ 0.001) were risk factors for OS.Cox multivariate analysis showed that middle-high risk or high risk of IPI (HR =2.138,95％ CI:1.301-3.512,P =0.001),refractory patients (HR =3.157,95％CI:1.001-10.644,P =0.014),failure to achieve CR or PR after salvage chemotherapy (HR=3.017,95％CI:2.218-7.366,P＜0.001),LDH increased (HR =2.236,95％ CI:1.797-2.781,P =0.001),large mass (HR =1.792,95％ CI:1.255-2.558,P ＜ 0.001) were independent risk factors affecting OS.Adverse reactions to chemotherapy were neutropenia,thrombocytopenia,nausea and vomiting,liver damage and cardiotoxicity,with no treatment-related death.Conclusion The second-line chemotherapy regimen containing gemcitabine combined with rituximab has a better curative effect on relapsed or refractory B-cell non-Hodgkin lymphoma,and the safety is good.Middle-high risk or high risk of IPI,refractory patients,failure to achieve CR or PR after salvage chemotherapy,elevated LDH and large mass were independent risk factors for OS.In patients with relapsed or refractory disease after rituximab treatment,re-application of rituximab was not effective.