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 impacts of isorhynchophylline （IRN） on airway inflammation in asthmatic mice by regulating the monocyte chemotactic protein-1 （MCP-1）/CC chemokine receptor 2 （CCR2） signaling pathway. METHODS The asthmatic mice model was established by injecting and inhaling ovalbumin. The successfully modeled mice were randomly grouped into asthma group， IRN low-dose group （IRN-L， intragastric administration of 10 mg/kg IRN）， IRN high-dose group （IRN-H， intragastric administration of 20 mg/kg IRN）， IRN-H+CCL2 group [intragastric administration of 20 mg/kg IRN+intraperitoneal injection of 7.5 ng CC chemokine ligand 2 （CCL2）] and positive control group （intraperitoneal injection of 2 mg/kg dexamethasone）. The mice injected and inhaled with sterile phosphate-buffered solution were included in the blank control group， with 10 mice in each group. The mice in administration groups were given relevant medicine once a day， for consecutive 2 weeks. The levels of airway hyperreactivity indexes such as enhanced （Penh） value， tumor necrosis factor-α （TNF-α），interleukin-13 （IL-13） and IL-4 in serum， the number of eosinophil （EOS）， lymphocyte （LYM） and neutrophils （NEU） in alveolar lavage fluid and the protein expressions of MCP-1 and CCR2 in lung tissue were observed in each group； the pulmonary histopathological changes were observed， and inflammatory cell infiltration score was evaluated. RESULTS Compared with the blank control group， the infiltration of inflammatory cells in the lung tissue of mice was more significant in the asthma group， and there was swelling and shedding of cells； inflammatory infiltration score， Penh value， the levels of IL-4， IL-13 and TNF-α， the number of EOS， NEU and LYM， the protein expressions of MCP-1 and CCR2 were increased significantly （P＜0.05）. Compared with the asthma group， the pathological injuries of the IRN-L group， IRN-H group and positive control group were improved， and the above quantitative indexes were decreased significantly （P＜0.05）. Compared with the IRN-L group， the above quantitative indexes of the IRN-H group and positive control group were decreased significantly （P＜0.05）. There was no statistical significance in the above quantitative indexes between the IRN-H group and the positive control group （P＞0.05）. Compared with the IRN-H group， the above quantitative indexes of the IRN-H+CCL2 group were increased significantly （P＜0.05）. CCL2 reversed the protective effect of high-dose IRN on asthmatic mice. CONCLUSIONS IRN may reduce the release of airway inflammatory factors in asthmatic mice by inhibiting the activation of the MCP-1/CCR2 signaling pathway， so as to achieve the purpose of improving asthma.

Diagnosis, Differential ; Head ; Humans ; Immunoglobulin G ; Mikulicz' Disease/diagnosis* ; Submandibular Gland

Esophageal Perforation ; Esophagus ; Foreign Bodies ; Humans

OBJECTIVE: To investigate clinical effects of intraoperative arthrography monitoring assisted closed reduction and internal fixation for intercondylar fracture of humerus in children. METHODS: From January 2013 to July 2018, 18 children with intercondylar fracture of humerus were treated by operation, including 13 males and 5 females aged from 3 to 12 years old with an average age of (8.50±2.57) years old. According to Toniolo & Wilkinson classification, 8 children were typeⅠand 10 children were typeⅡ. During the operation, closed reduction and internal fixation were performed under the monitoring of intraoperative radiography, open reduction and internal fixation were performed in necessity. Mayo score of elbow joint was used to evaluate clinical effect at 6 months after operation. RESULTS: All children were underwent arthrography monitoring during operation, 5 children were treated with closed reduction and internal fixation for intraoperative arthrography found no fracture of articular cartilage, 11 children by closed reduction and internal fixation because of fracture of articular cartilage involving the joint space with displacement less than 2 mm, and 2 children by closed or open reduction and internal fixation for fracture of articular cartilage surface with displacement above 2 mm, which 1 child with smooth of joint surface was performed closed reduction and internal fixation, 1 child without smooth of joint surface and displacement above 2 mm was performed open reduction and internal fixation. All children were followed up from 8 to 26 months with an average of (20.28±4.40) months. All factures were healed from 6 to 9 weeks with an average of (7.33±0.77) weeks. Postoperative Mayo score of elbowjoint at 6 months was (89.44±11.36), and 12 patients got excellent results, 5 good and 1 poor. One patient occurred partial limitation of flexion or extension of elbow joint. No elbow deformity and other complications occurred. CONCLUSION The treatment of intercondylar fracture of humerus in children under monitoring of intraoperative radiography could reduce opertaion injuries and complications, confirm the reduction effect of articular surface of cartilage in time and clearly, and promote recovery of elbow joint function.
Arthrography ; Child ; Child, Preschool ; Female ; Fracture Fixation, Internal ; Humans ; Humeral Fractures/surgery* ; Humerus ; Male ; Treatment Outcome

BACKGROUND: Intensive therapy with disease modifying anti-rheumatic drugs (DMARDs) has been reported to improve the outcomes of rheumatoid arthritis (RA). However, real-world study on the effect of intensive therapy on RA sustained remission is still lacking. This study aimed to investigate the outcome of sustained intensive DMARD therapy (SUIT) for RA in a real-world 5-year consecutive cohort. METHODS: Based on a consecutive cohort of 610 out-patients with RA, remission of RA was assessed in 541 patients from 2012 to 2017, by dividing into SUIT, non-SUIT, and intermittent SUIT (Int-SUIT) groups. Changes in the disease activity scores were evaluated by 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR), 28-joint disease activity score based on C-reactive protein (DAS28-CRP), and clinical deep remission criteria (CliDR). Cumulative remission rates between different groups were compared using Kaplan-Meier curves and predictive factors of sustained remission were identified by univariate and multivariate logistic regression analysis. RESULTS: The remission rates of the SUIT group decreased from 12.0% (65/541) to 5.6% (20/359) based on DAS28-ESR, from 14.0% (76/541) to 7.2% (26/359) based on DAS28-CRP, and from 8.5% (46/541) to 3.1% (11/359) based on CliDR, respectively, with a gradually decreasing trend during the 5 years. The SUIT regimen led to a significantly higher cumulative remission rate than non-SUIT regimen based on DAS28-ESR (39.7% vs. 19.5%, P = 0.001), DAS28-CRP (42.0% vs. 19.6%, P = 0.001), and CliDR (24.5% vs. 8.7%, P = 0.001). The cumulative remission rates of patients treated with SUIT regimen were significantly higher than those treated with Int-SUIT regimen based on DAS28-ESR (39.7% vs. 25.7%, P = 0.043) and CliDR (24.5% vs. 14.2%, P = 0.047), but there was no significant difference between the two groups based on DAS28-CRP (42.0% vs. 27.4%, P = 0.066). Multivariate logistic regression analysis showed that the use of SUIT regimen was an independent favorable predictor according to different remission definitions (for DAS28-ESR: odds ratio [OR], 2.215, 95% confidence interval [CI]: 1.271-3.861, P = 0.005; for DAS28-CRP: OR, 1.520, 95% CI: 1.345-1.783, P = 0.002; for CliDR: OR, 1.525, 95% CI: 1.314-1.875, P = 0.013). CONCLUSION Sustained intensive treatment of RA is an optimal strategy in daily practice and will lead to an increased remission rate.

Inhibition of cytochrome P450 (CYP450) enzymes is the most common reasons for drug interactions, so the study on early prediction of CYPs inhibitors can help to decrease the incidence of adverse reactions caused by drug interactions.CYP450 2E1(CYP2E1), as a key role in drug metabolism process, has broad spectrum of drug metabolism substrate. In this study, 32 CYP2E1 inhibitors were collected for the construction of support vector regression (SVR) model. The test set data were used to verify CYP2E1 quantitative models and obtain the optimal prediction model of CYP2E1 inhibitor. Meanwhile, one molecular docking program, CDOCKER, was utilized to analyze the interaction pattern between positive compounds and active pocket to establish the optimal screening model of CYP2E1 inhibitors.SVR model and molecular docking prediction model were combined to screen traditional Chinese medicine database (TCMD), which could improve the calculation efficiency and prediction accuracy. 6 376 traditional Chinese medicine (TCM) compounds predicted by SVR model were obtained, and in further verification by using molecular docking model, 247 TCM compounds with potential inhibitory activities against CYP2E1 were finally retained. Some of them have been verified by experiments. The results demonstrated that this study could provide guidance for the virtual screening of CYP450 inhibitors and the prediction of CYPs-mediated DDIs, and also provide references for clinical rational drug use.