Iodine status and its association with prevalence of thyroid diseases in adults from Jiangxi Province, China.

BACKGROUND: Iodine is an essential element for the biosynthesis of thyroid-stimulating hormone (TSH). Both excessive and deficient iodine are major risk factors for thyroid diseases, including thyroid dysfunction, thyroid nodules, and thyroid autoimmunity (TAI). This study aimed to elucidate the relationship between iodine status and the prevalence of thyroid diseases through a national cross-sectional epidemiological survey in Jiangxi province (China). METHODS: This population-based, cross-sectional study enrolled 2636 Chinese local inhabitants who aged over 18 years old from April to August in 2015. Physical examination was performed and biochemical indices, urinary iodine concentration (UIC), and TSH level were measured. The Chi-square test, nonparametric test, and 4 multivariate logistic regression models adjusted for risk factors were applied to analysis. Spearman correlation coefficients were calculated to investigate the relationship between iodine intake level and the prevalence of thyroid diseases. RESULTS: The median UIC was 176.4 µg/L, and a significant difference was found in median UIC between men (182.45 µg/L) and women (169.25 µg/L) (P = 0.03). Among these study subjects, 14.4%, 44.5%, 26.1%, and 15.0% had deficient, adequate, more than adequate, and excessive iodine concentrations, respectively. The prevalence rates of hyperthyroidism, subclinical hyperthyroidism, hypothyroidism, subclinical hypothyroidism, thyroid nodules, and TAI were 0.91%, 0.57%, 0.34% and 7.89%, 9.45%, and 12.7%, respectively. Significant differences were found in iodine status, waist circumstance, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), TSH, thyroid nodules, and TAI between men and women (P < 0.05). Compared with those with adequate UIC, subjects with excessive UIC had higher prevalence rates of thyroid dysfunction (odds ratio (OR) = 1.74, 95% confidence interval (CI): 1.40-2.54) and thyroid nodules (OR = 3.33, 95%CI 1.32-8.42). In addition, subjects with deficient and excessive UIC were at the higher risk of TAI compared with those with adequate UIC (OR = 1.68, 95%CI: 1.19-2.60; OR = 1.52, 95%CI: 1.04-2.96, respectively). UIC was positively correlated with the prevalence rates of thyroid nodules (r = -0.44, P < 0.01) and TAI (r = -0.055, P < 0.01). On the contrary, UIC was negatively correlated with the risk of thyroid dysfunction (r = -0.24, P > 0.05). CONCLUSION: Adult inhabitants from Jiangxi province in the TIDE study were in the adequate iodine status. Excessive iodine status was noted as a risk factor for thyroid dysfunction and thyroid nodules. In addition, both iodine deficiency and excessive iodine were risk factors for TAI.

Renal venous sampling assisted the diagnosis of juxtaglomerular cell tumor: a case report and literature review.

Juxtaglomerular cell tumor (JCT) is an endocrine tumor marked by elevated renin levels and high blood pressure. This case report presents the clinical findings of a 47-year-old woman with a history of recurrent hypokalemia, headaches, hypertension, and increased plasma renin activity (PRA). Dynamic enhanced magnetic resonance imaging (MRI) revealed a small nodule on the upper part of the right kidney. Selective renal venous sampling indicated a higher PRA only in the right upper pole renal vein. The patient underwent surgical removal of the right kidney mass, and the pathology results confirmed the diagnosis of JCT. This case underscores the importance of conducting selective renal venous sampling for accurate JCT diagnosis.

Genomic and Transcriptomic Characterization of Natural Killer T Cell Lymphoma.

Natural killer/T cell lymphoma (NKTCL) is an aggressive and heterogeneous entity of non-Hodgkin lymphoma, strongly associated with Epstein-Barr virus (EBV) infection. To identify molecular subtypes of NKTCL based on genomic structural alterations and EBV sequences, we performed multi-omics study on 128 biopsy samples of newly diagnosed NKTCL and defined three prominent subtypes, which differ significantly in cell of origin, EBV gene expression, transcriptional signatures, and responses to asparaginase-based regimens and targeted therapy. Our findings thus identify molecular networks of EBV-associated pathogenesis and suggest potential clinical strategies on NKTCL.

Prevalence and associated factors of metabolic syndrome in adults: a population-based epidemiological survey in Jiangxi province, China.

BACKGROUND: Metabolic syndrome (MS) has abruptly increased in China in the past two decades, gradually representing an important public health threat over the years. Here, we firstly reported the prevalence and associated factors of metabolic syndrome in Jiangxi province, China. METHODS: A population-based cross-sectional survey was performed in Jiangxi province, China, from April to August 2015. MS was diagnosed by International Diabetes Federation (IDF) and Chinese Diabetes Society (CDS) criteria, respectively. Factors associated with MS were investigated by multivariate logistic regression. RESULTS: A total of 2665 residents aged over 18 years were enrolled, and 2580 effectively participated. According to IDF and CDS criteria, age-standardized prevalence of MS were 21.1 and 15.2% in all participants, respectively; prevalence were 19.6% or 17.1% in men, and 22.7% or 13.0% in women, based on these respective criteria. Rural participants had a significantly higher prevalence than urban individuals, so did rural females. Prevalence in males did not differ between rural and urban participants. Factors independently associated with MS were low education level and menopausal state. CONCLUSIONS: To the best of our knowledge, this was the latest study on MS prevalence in Jiangxi province. In conclusion, MS prevalence is high in Jiangxi province. Considering the unhealthy lifestyle, education is urgently needed to prevent the rapid increase of MS prevalence.

[Effect of miR-214 on Fludarabine Resistance in Chronic Lymphocytic Leukemia].

OBJECTIVE: To investigate effect and mechanism of miR-214 in fludarabine resistance of chronic lympho-cytic leukemia (CLL). METHODS: A total of 10 patients with CLL resistante to fludarabine (Flu) and 10 healthy persons admitted to Hematology Department of our hospital in August 2014 - July 2018 were selected. Expression level of miR-214 in mononuclear cells in patients with CLL and healthy persons were determined by RT-PCR. Primary CLL cells from patients with CLL were divided into normal control group (control group), negative control group (miR-214-NC group) and viral transinfection group (miR-214-ASO group). After 24 h-transfection, CLL cells were cultured with different con-centration of Flu for 48 h, then the cell proliferation and apoptosis were detected, and the levels of down-stream genes and proteins releted with PTEN and PI3K/AKT signialing pathway were determined. RESULTS: The expression level of miR-214 in mononuclear cells of CLL patients significantly increased in comparison with healthy persons(P<0.05); the expression level of miR-214 in miR-214-ASO group significantly decreased (P<0.05); Absorbance in control group at Flu concentration of 3, 10 and 30 µmol/L was significantly decreased (P<0.05). Apoptosis rate in miR-214-ASO group at Flu concentration of 10 mmol/L significantly increased (P<0.05). At Flu concentration of 10 mmol/L, mRNA levels PTEN and BAD in miR-214-ASO group significantly increased (P<0.05), but mRNA levels of MDM2 and NF-κB significantly decreased (P<0.05). At Flu concentration of 10 mmol/L, protein levels of PTEN and p-BAD in miR-214-ASO group significantly increased (P<0.05), but protein levels of MDM2 and NF-κB significantly decreased (P<0.05). CONCLUSION: Inhibition of miR-214 can enhance the sensitivity of drug-resistant CLL cells to fludarabine, which may be raleted with the promotion of cell apotosis and regulation of down-stream molecules expression of PTEN/AKT signaling pathway.

[Influence of Chromosome Abnormality on Therapeutic Efficacy and Prognosis of Newly Diagnosed Multiple Myeloma Treated with Bortezomib].

OBJECTIVE: To explore the influence of chromosome abnormality on therapeutic efficacy and prognosis of patients with newly diagnosed multiple myeloma(MM) treated with bortezomib. METHODS: The clinical data of 152 patients with newly diagnosed MM were collected from January 2008 to December 2011. All patients received bortezo-mib-based chemotherapy and the therapeutic efficacy were investigated for 4 cycles later. The R banding and DNA probe were used to analyze the chromosome and gene (RB1 deletion, D13S319 deletion, P53 deletion, IgH rearrangement and 1q21 amplification) of chromosome specimens. Moreover, the therapeutic efficacy and long-term survival data were analyzed among the patients with different types of chromosomal abnormality. The Kaplan-Meier was applied to analyze survival, and COX risk proportional model was used for multivariate analysis. RESULTS: Among 152 patients with MM, there were 47 cases(30.92%) of abnormal karyotype, 43 cases(28.29%) of abnormal RB1,49 cases (32.24%) of abnormal D13S319, 30 cases (19.74%) of abnormal P53, 58 cases (38.16%) of abnormal IgH and 33 cases (21.71%) of abnormal chromosome 1q21. All the patients were evaluable for the therapeutic efficacy, including 24 CR, 54 nCR, 21 PR, 14 MR and 39 PD with response rate of 74.34% and remission rate of 50.66%. Compared with normal controls, the response and remission rate were lower than that in the patients with abnormal karyotype of D13S319, P53 or IgH, and remission rate was lower in the patients with RB1 or 1q21 (P<0.05). All the patients were followd-up (median: 52.0 months, range: 22-72 months), but median overall survival(OS) was not yet reached at the end of the follow-up. The median OS was in the patients with different chromosome versus the normal subjects (P<0.05). The chromosome abnormality was found to affect the prognosis of MM by COX multivariate analysis. In regard to the normal subjects, the risk for poor prognosis increased by 1.177, 2.639, 6.552, 3.124, 2.045 and 7.264 fold in the patients with abnormal Karyotype of RB1, D13S319, P53, IgH and 1q21, respectively. CONCLUSION: The abnormality of chromosome can influence the efficacy and prognosis of newly diagnosed MM patients treated with bortezomib. The detection of chromosomal abnormalities has a certain reference value for the treatment of primary MM.

Thermodynamics and Structural Evolution during a Reversible Vesicle-Micelle Transition of a Vitamin-Derived Bolaamphiphile Induced by Sodium Cholate.

Interaction of endogenous sodium cholate (SC) with dietary amphiphiles would induce structural evolution of the self-assembled aggregates, which inevitably affects the hydrolysis of fat in the gut. Current work mainly focused on the interaction of bile salts with classical double-layered phospholipid vesicles. In this paper, the thermodynamics and structural evolution during the interaction of SC with novel unilamellar vesicles formed from vitamin-derived zwitterionic bolaamphiphile (DDO) were characterized. It was revealed that an increased temperature and the presence of NaCl resulted in narrowed micelle-vesicle coexistence and enlarged the vesicle region. The coexistence of micelles and vesicles mainly came from the interaction of monomeric SC with DDO vesicles, whereas micellar SC contributed to the total solubilization of DDO vesicles. This research may enrich the thermodynamic mechanism behind the structure transition of the microaggregates formed by amphiphiles in the gut. It will also contribute to the design of food formulation and drug delivery system.

Effect of Pin1 inhibitor juglone on proliferation, migration and angiogenic ability of breast cancer cell line MCF7Adr.

This study aimed to evaluate the effects of Pin1 inhibitor Juglone on proliferation, migration and the angiogenic ability of breast cancer cell line MCF7Adr. MCF7Adr cells were cultured and separately treated with Pin1 inhibitor Juglone (treatment group) and DMEM without drug (control group). The cell cycle was examined by flow cytometry. Cell migration was measured by wound-healing assay. Cyclin E protein content was detected by Western blotting. The angiogenesis factor vascular endothelial growth factor (VEGF) in cell media was determined by enzyme linked immunosorbent assay. The results showed that the percentage of cells in G2/M phase in treatment group was significantly higher than that in control group (25.5% vs. 10.1%, P<0.05), and that in G0/G1 phase and S stage in treatment group was significantly lower than that in control group (40.5% vs. 48.2%, and 33.7% vs. 41.7%, P<0.05). Cyclin E protein content in treatment group was significantly lower than that in control group (39.2 ± 7.4 vs. 100 ± 23.1, P<0.05). (A0-A24)/A0 value in treatment group was significantly lower than that in control group (23.9 ± 3.8 vs. 100 ± 14.4, P<0.05). VEGF-A, -B, and -C contents in cell media of treatment group were significantly lower than those in control group (P<0.05). It was suggested that Pin1 inhibitor Juglone can effectively inhibit the proliferation, migration and the angiogenic ability of MCF7Adr cells, and can be used as an alternative drug therapy for breast cancer.

Tracing type 1 diabetic Tibet miniature pig's bone marrow mesenchymal stem cells in vitro by magnetic resonance imaging (1).

BACKGROUND: Traditional cell-tracking methods fail to meet the needs of preclinical or clinical research. Thus, the aim of the present study was to establish a new method of double labeling bone marrow mesenchymal stem cells (BMSCs) from type 1 diabetic (T1D) minipigs with super-paramagnetic iron oxide (SPIO) and enhanced green fluorescent protein (eGFP) and tracing them using MRI in vitro. METHODS: Isolated BMSCs from T1D minipigs were labeled with eGFP and different concentrations of SPIO. The effects of lentivirus (LV)-eGFP transfection and SPIO on the viability and growth curves of BMSCs were determined by Trypan blue exclusion, the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay and flow cytometry. Cellular ultrastructure was evaluated by transmission electron microscopy. Magnetic resonance imaging was used to evaluate BMSCs labeled with SPIO-eGFP complexes 6 weeks after labeling. RESULTS: Expression of eGFP in BMSCs peaked 96 h after transfection with LV-eGFP. Prussian blue staining revealed scattered blue granules in the cytoplasm of SPIO-labeled cells. Transmission electron microscopy revealed that the dense granules aggregated mainly in secondary lysosomes. On MRI, T2* -weighted imaging was far more sensitive for SPIO-labeled BMSCs than other image sequences 3 and 6 weeks after the cells had been labeled with SPIO-eGFP. CONCLUSIONS: We have developed a relatively simple and safe method for double labeling of BMSCs from T1D minipigs using SPIO and LV-eGFP and tracing them in vitro by MRI for 6 weeks.

[Autoimmune hemolytic anemia associated with B-cell chronic lymphoproliferative disorders].

This study was purpose to investigate the clinical characteristics of B-cell chronic lymphoproliferative disorders (B-CLPD) complicated by autoimmune hemolytic anemia (AIHA) so as to improve the understanding of this disease. The clinical characteristics, laboratory data, therapy and outcome of 14 patients suffering from B-CLPD complicated by AIHA were retrospectively analyzed in Wuxi People Hospital and the First Affiliated Hospital of Nanjing Medical University from 2000 to 2012. The results showed that 9 cases of the 14 patients were patients with chronic lymphocytic leukemia (CLL), 5 cases were patients with lymphoma, at time of hemolysis the median level of hemoglobin was 61 (33 - 84)g/L, the median ratio of reticulocytes was 12.0 (3.1 - 35.0)%, the positive rate of Coombs test was 100%. 1 case received corticosteroid alone, 5 cases were treated with chemotherapy combined with corticosteroid, 8 cases were treated with immunochemotherapy rituximab combined with corticosteroid. Overall response rate was 100%, in which CR was 78.6% (11/14), PR was 21.4% (3/14). The follow-up for these patients were performed to now, 35.7% (5/14) patients relapsed with hemolysis again, but they showed therapeutic response to treatment with above-mentioned therapy. From patients treated with rituximab alone, only 1 patient relapsed. Among 14 patients, 6 cases died, 1 case was lost, the other cases are still alive. It is concluded that the AIHA is the commonest complication of B-CLPD, it can be observed at different stages of B-CLPD, the treatment with corticosteroids can give well therapeutic effect for these patients, but the long time CR is lower, the rituximab has been confirmed to be effective for B-CLPD complicated by AIHA.

[Polymorphisms of FcγRIIA, FcγRIIIA and FcγRIIB in patients with immune thrombocytopenia and their clinical significance].

This study was aimed to investigate the correlation of FcγR polymorphisms with the susceptibility, severity and efficacy of immunotherapy for patients with immune thrombocytopenia (ITP). PCR and DNA sequencing were used to determine the polymorphisms of FcγRIIA, FcγRIIIA and FcγRIIB in 44 ITP patients, and in 97 healthy control subjects. The results indicated that FcγRIIIA-158V/F polymorphisms between patients and controls were statistically significantly different (P = 0.015); among FcγRIIIA genotypes, the frequency of 158V/V homotype was higher in ITP (P = 0.005). However, the FcγRIIA-131H/R or FcγRIIB-232T/I polymorphisms were not significantly different between patients and controls; there were no correlation of FcγRIIA, FcγRIIIA and FcγRIIB genotype frequencies with the platelet counts or the courses of ITP; among the 38 ITP patients who received treatments, the complete response (CR) rate was 42% (16/38), and partial response (PR) rate was 34% (13/38). The therapeutic response was significantly different between FcγRIIIA-158V/V homotype and 158F/V heterotype (P = 0.034). The CR of patients with 158V/V homotype was obviously lower than that of patients with 158F/V, but the frequencies of FcγRIIA and FcγRIIB genotypes not correlated with the responsiveness to treatment. The CR rate of 6 patients treated with rituximab was 67%, and PR rate was 17%. The overall response rate was as high as 84%, the adverse reactions were not observed. It is concluded that the polymorphism of FcγRIIIA-158V/F, but not FcγRIIA-131H/R or FcγRIIB-232T/I, correlates with the patient susceptibility and therapeutic response of ITP.

[Research advances on correlation of ARID5B gene with childhood acute lymphoblastic leukemia - review].

Childhood acute lymphoblastic leukemia (C-ALL) is the most common pediatric cancer. Although its etiology remains poorly understood, the hypothesis of ALL correlated with a genetic basis was examined through association studies based on candidate genes. Recently, two independent large-scale genome-wide association studies reported that the five single nucleotide polymorphisms (rs7073837; rs10821936; rs10994982; rs7089424; rs10740055) in the gene AT rich interactive domain 5B (ARID5B) at 10q21.2, were associated with the high incidence risk of C-ALL, especially with hyperdiploid lymphoblastic leukemia. Variations in these single nucleotide polymorphisms influence the risk of specific disease subtypes, and also possess race- and sex-differences in leukemia incidence. Further elucidation of the mechanisms through which ARID5B variants are involved in C-ALL not only has a great diagnostic value, but also a guidance for the clinical therapy, ultimately improving the prognosis of disease. Therefore, the related studies of ARID5B with C-ALL were summarized briefly in this review.

Increased frequency and clinical significance of myeloid-derived suppressor cells in human colorectal carcinoma.

AIM: To investigate the frequency and clinical significance of the myeloid-derived suppressor cells (MDSC) in human colorectal carcinoma (CRC). METHODS: Samples of peripheral blood and tumor tissue from 49 CRC patients were analyzed. Mononuclear cells were isolated by Ficoll-Hypaque density gradient centrifugation and were subjected to a flow cytometry-based immunophenotypic analysis. RESULTS: A considerable increase in the percentage of CD33⁺HLA-DR⁻ MDSCs was observed in the peripheral blood (1.89% ± 0.75%) and tumor tissues (2.99% ± 1.29%) of CRC patients as compared with that in the peripheral blood of healthy controls (0.54% ± 0.35%). This expanded CD33⁺HLA-DR⁻ subset exhibited immature myeloid cell markers, but not lineage markers, and showed up-regulation of CD18/CD11b expression as compared with the MDSCs from healthy donors. Further studies showed that the MDSC proportion in CRC peripheral blood was correlated with nodal metastasis(P = 0.023), whereas that in tumor tissues was correlated with nodal/distant metastasis (P = 0.016/P = 0.047) and tumor stage (P = 0.028), suggesting the involvement of MDSCs in CRC tumor development. CONCLUSION: Characterization of MDSCs in CRC suggests the clinical significance of circulating and tumor-infiltrating MDSCs and may provide new insights into the CRC immunotherapy targeting MDSCs.

JAK2 V617F, MPL W515L and JAK2 Exon 12 Mutations in Chinese Patients with Primary Myelofibrosis.

OBJECTIVE: JAK2 V617F, MPL W515L and JAK2 exon 12 mutations are novel acquired mutations that induce constitutive cytokine-independent activation of the JAK-STAT pathway in myeloproliferative disorders (MPD). The discovery of these mutations provides novel mechanism for activation of signal transduction in hematopoietic malignancies. This research was to investigate their prevalence in Chinese patients with primary myelofibrosis (PMF). METHODS: We introduced allele-specific PCR (AS-PCR) combined with sequence analysis to simultaneously screen JAK2 V617F, MPL W515L and JAK2 exon 12 mutations in 30 patients with PMF. RESULTS: Fifteen PMF patients (50.0%) carried JAK2 V617F mutation, and only two JAK2 V617F-negative patients (6.7%) harbored MPL W515L mutation. None had JAK2 exon 12 mutations. Furthermore, these three mutations were not detected in 50 healthy controls. CONCLUSION: MPL W515L and JAK2 V617F mutations existed in PMF patients but JAK2 exon 12 mutations not. JAK2 V617F and MPL W515L and mutations might contribute to the primary molecular pathogenesis in patients with PMF.

[Isocitrate dehydrogenase gene mutations in acute myeloid leukemia].

The purpose of this study was to identify point mutation of the isocitrate dehydrogenase gene (IDH1 and IDH2) in patients with acute myeloid leukemia(AML) and its clinical significance. 90 de novo AML patients were selected for this study, the genomic DNA was served as template, the exon4 of IDH1 and IDH2 were amplified respectively. The IDH mutation was detected by using directly sequencing method for PCR product. The results indicated that among 90 de novo AML patients, 4 patients (4.4%) showed the IDH1 gene mutation positive, and 7(7.8%) patients showed IDH2 gene mutation positive. None was found harboring both mutations, the overall rate of mutation positive of them was 12.2%. In the AML patients with IDH gene mutation positive, the rate of normal karyotype was 72.7%, which was significantly higher than that in abnormality karyotype. The CR rate in mutation positive patients was 72.7%, which seemed as if higher than that in mutation negative patients, but without statistical significance. The mutation disappeared when the patients gained CR, and reappeared in same loci after relapse occurred. It is concluded that the IDH gene point mutation appears in normal karyotype patients, especially in patients combined with NPM1 gene mutation. The IDH gene mutation may be an important target for therapy and evaluating clinical prognosis of patients with normal karyotype.

[A study of tracking the superparamagnetic iron oxide and enhanced green fluorescent protein labeled miniature porcine bone marrow stem cells by in vitro MRI].

OBJECTIVES: To track bone marrow stem cells (BMSCs) labeled by enhanced green fluorescent protein (EGFP) and superparamagnetic iron oxide (SPIO)-poly-L-lysine (PLL) compound by MRI in vitro for autotransplantation into pancreas of type 1 diabetes miniature pigs. METHODS: The BMSCs were isolated by density gradient centrifugation and attachment culture from type 1 diabetes minipigs' bone marrow. Expressional intensity of EGFP in BMSCs transfected lentivirus-EGFP with a multiplicity of infection (MOI) of 30:1 reached the highest level after 96 h from transfection, while the positive rate was 43.2%. Different magnetic resonance scanning protocols were carried out on various density BMSCs labeled by different concentration of SPIO in various time-point in vitro. RESULTS: When SPIO concentration was 25 mg/L (count in Fe(3+)), the positive Fe(3+)-labeling rate of BMSCs was 93.1%. Most of SPIO particles in BMSCs' cytoplasm were observed in secondary lysosomes, but they were not detected in important organelle as cell nucleus. Comparing with gelatin the MRI of BMSCs labeled with SPIO in the condition with 1 × 10(4)/ml cells density and 25 mg/L Fe(3+) concentration in vitro, the signal intensity changes (ΔSI) after BMSCs labeled with SPIO 3 weeks and 6 weeks in TSE T(1)WI, TSE T(2)WI and FLASH T(2) WI sequences were 12%, 41%, 63% and 7%, 28%, 46% respectively (P < 0.01 and P < 0.05, respectively). CONCLUSIONS: The data showed that the porcine BMSCs labeled with SPIO and EGFP could be traced successfully in vitro by MRI in the suitable sequences.

[The functional analysis of glucokinase gene E339K mutation].

OBJECTIVE: To explore the molecular mechanisms of glucokinase (GCK) E339K mutation resulting in maturity-onset diabetes of the young-2 (MODY2). METHODS: Fasting plasma glucose (FPG), oral glucose tolerance test (OGTT) overload 2 h glucose (2hPG), glycosylated hemoglobin A1c (HbA1c) and fasting insulin (FIns) level were measured, respectively. Mutant glutathione S-transferase (GST)-GCK-cDNA was constructed with site-directed mutagenesis. Wild type and mutant GCK protein expressed in E. Coli were purified with affinity chromatography. Enzymatic kinetics and thermal stability were tested with enzyme-coupled analysis. RESULTS: Compared with non-mutants, mutants had higher FPG [(6.92±0.95) mmol/L vs (4.70±0.35) mmol/L, P<0.001] 2hPG [(9.00±1.49) mmol/L vs (5.51±0.86) mmol/L, P<0.001], HbA1c [(6.46±0.69)% vs (4.83±0.30)%, P<0.01], and lower FIns level [(6.15±1.97) mIU/L vs (10.79±4.93) mIU/L, P<0.01], HOMA-ß (34.16±3.62 vs 172.53±76.58, P<0.001). This mutation induced lower protein yield [(12.7±1.72) mg/L vs (16.2±2.65) mg/L, P<0.01], lower appetency for glucose [S0.5: (13.96±1.89) mmol/L vs (5.92±0.99) mmol/L, P<0.001] and ATP [Km:(3.27±1.14) mmol/L vs (0.30±0.09) mmol/L, P<0.001], lower catalytic ability [Kcat: (1.62±0.35)/s vs (25.18±2.10)/s, P<0.001]. It also showed protein thermal instability. CONCLUSION: Glucokinase gene E339K mutation promotes the development of MODY2 by affecting protein yield and protein stability as well as the enzymatic kinetics of GCK.

[Mutation of tet2 gene and malignant blood disease].

Tet2 (the 2nd member of tet oncogene family) is a newly discovered antioncogene on the chromosome 4q24 of the patient with malignant myeloma, which has a potential for functional deletion. Recent studies demonstrated that tet2 mutation was found in polycythemia vera (PV), essential thrombocythemia (ET), myelofibrosis, systematic mastocytosis (SM), and myelodysplastic syndrome (MDS). However, a great number of perspective researches are still needed for exploring the role of tet2 in the pathogenesis of malignant blood diseases. In this review, the relation of tet2 mutation with myeloproliferative neoplasm, systemic mastocytosis, myelodysplastic syndrome, acute myeloid leukemia and other malignant blood diseases are summarized.