The novel HLA-B*48:01:11 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*48:01:11 differs from HLA-B*48:01:01:01 by one nucleotide in exon 4.

Mini-LED, Micro-LED and OLED displays: present status and future perspectives.

Presently, liquid crystal displays (LCDs) and organic light-emitting diode (OLED) displays are two dominant flat panel display technologies. Recently, inorganic mini-LEDs (mLEDs) and micro-LEDs (µLEDs) have emerged by significantly enhancing the dynamic range of LCDs or as sunlight readable emissive displays. "mLED, OLED, or µLED: who wins?" is a heated debatable question. In this review, we conduct a comprehensive analysis on the material properties, device structures, and performance of mLED/µLED/OLED emissive displays and mLED backlit LCDs. We evaluate the power consumption and ambient contrast ratio of each display in depth and systematically compare the motion picture response time, dynamic range, and adaptability to flexible/transparent displays. The pros and cons of mLED, OLED, and µLED displays are analysed, and their future perspectives are discussed.

[Relationship between TET2 Gene SNP rs3733609 C/T and JAK2V617F Allele Burden in Patients with Myeloproliferative Neoplasms].

OBJECTIVE: To investigate the relationship between the polymorphism of TET2 gene SNP rs3733609 and JAK2V617F allele burden in patients with myeloproliferative neoplasms (MPN). METHODS: The exon 9 of TET2 gene was amplified by RT-PCR, and the nucleotide sequence of SNP rs3733609 site was analyzed by gene sequencing. The MGB Taqman probe PCR method was used to detect the JAK2V617F allele burden. The correlation of TET2 gene SNP rs3733609 C/T with the JAK2V617F allele burden and clinical parameters was analyzed. RESULTS: TET2 gene rs3733609 C/T heterozygosity (normal T/T) could be detected in 19 cases of 85 cases of JAK2V617F positive MPN (22.4%) patients, while the TET2 gene rs3733609 C/T heterozygosity could be detected only in 9 of the 106 healthy volunteers, and the incidence was only 8.5% (9/106). Compared with the negative group (TET2 rs3733609 T/T), there was no significant difference in the median age, hemoglobin level and platelet count in the patients with TET2 gene SNP rs3733609 (CT/TC) positive, but the WBC count of peripheral blood and JAK2V617F allele burden significantly increased. In JAK2V617F high allele burden group, TET2 gene SNP rs3733609 was positive in 7 cases (36.8%, 7/19), the ratio was higher than that in the low allele burden group(18.2%, 12/66). CONCLUSION: TET2 SNP rs3733609 C/T may be a new susceptible allelee, which affects the clinical characteristics and clonal evolution of MPN patients.

Two novel compound heterozygous mutations associated with types I and II protein C deficiency with unusual phenotypes.

INTRODUCTION: We diagnosed two Chinese hereditary PC deficiency families and identified two novel compound heterozygous mutations (p.Arg194Cys/Gly324Ser and p.Glu274X/Asp297His) in the protein C (PROC) gene. The probands were classified as types I and II PC deficiency. The aim of this article is to access the influence of the mutations on PC activity, antigen and protein structure, and to evaluate whether there is abnormal PC localization. MATERIALS AND METHODS: Genomic DNA of all family members was extracted, PCR amplified, and sequenced. The mutant PC expression plasmids were constructed. Expression assays, intracellular localization, and molecular modeling were performed. RESULTS: Proband 1, a type II PC defect, harbored a compound heterozygous mutation, p.Arg194Cys/Gly324Ser in the PROC gene, underwent two thromboembolic events. Expression assays indicated that the p.Arg194Cys mutant lead to decreased PC activity and normal PC Ag levels. Intracellular localization showed that both p.Arg194Cys and p.Gly324Ser co-localized with the endoplasmic reticuli and the Golgi apparatus. Molecular modeling suggested that the p.Gly324Ser mutation disturbed the interaction between the heavy and light chains of the PC protein. Proband 2, a type I PC defect, harbored a compound heterozygous PROC gene mutation, p.Glu274X/Asp297His, presented with recurrent spontaneous abortion and right popliteal vein thrombosis. Expression results were in accordance with the PC changes of the patient, and existed in defective PC transport. Structural model suggested p.Glu274X lead to disulfide bond between heavy and light chain cannot form. CONCLUSIONS: Our results confirm that two novel compound heterozygous PROC gene mutations are causative on the two PC deficiency families.

A TET2 rs3733609 C/T genotype is associated with predisposition to the myeloproliferative neoplasms harboring JAK2(V617F) and confers a proliferative potential on erythroid lineages.

Common germline single-nucleotide polymorphisms (SNPs) at JAK2 locus have been associated with Myeloproliferative neoplasms (MPN). And, the germline sequence variant rs2736100 C in TERT is related to risk of MPN, suggesting a complex association between SNPs and the pathogenesis of MPN. Our previous study (unpublished data) showed that there was a high frequency distribution in rs3733609 C/T genotype at Ten-Eleven Translocation 2 (TET2) locus in one Chinese familial primary myelofibrosis. In the present study, we evaluate the role and clinical significance of rs3733609 C/T genotype in JAK2V617F-positive sporadic MPN (n = 181). TET2 rs3733609 C/T genotype had a higher incidence (13.81%; 25/181) in JAK2V617F-positive sporadic MPN patients than that in normal controls (n = 236) (6.35%; 15/236), which was predisposing to MPN (odds ratio(OR) = 2.361; P = 0.01). MPN patients with rs3733609 C/T genotype had increased leukocyte and platelets counts, elevated hemoglobin concentration in comparison with T/T genotype. Thrombotic events were more common in MPN patients with rs3733609 C/T than those with T/T genotype (P < 0.01). We confirmed that rs3733609 C/T genotype downregulated TET2 mRNA transcription, and the mechanism may be involved in a disruption of the interaction between CCAAT/enhancer binding protein alpha (C/EBPA) and TET2 rs3733609 C/T locus.TET2 rs3733609 C/T genotype stimulated the erythroid hematopoiesis in MPN patients. Altogether, we found a novel hereditary susceptible factor-TET2 rs3733609 C/T variant for the development of MPN, suggesting the variant may be partially responsible for the pathogenesis and accumulation of MPN.

Analysis of clinical and laboratory characteristics in 42 patients with thrombotic thrombocytopenic purpura from a single center in China.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by microvascular platelet deposition and thrombus formation with resulting microangiopathic hemolytic anemia. Deficiency of the von Willebrand factor cleavage protease, also known as ADAMTS 13, has been implicated as an important etiological factor in TTP. Little studies were obtained on Chinese patients with TTP until now. Our aim was to analyze the clinical features, outcome and laboratory characteristics of Chinese TTP patients, and determine whether plasma ADAMTS 13 activity is decreased in TTP and its diagnostic value for TTP. Forty-two TTP patients (29 females; 13 males) admitted to our hospital from 1998 to 2010 were analyzed. There were 34 patients (81%) with the triad of TTP, including hemolytic anemia, thrombocytopenia and neurologic abnormalities; 7 (16.7%) had the classical pentad of TTP. Major etiologic factors were acquired autoimmunological abnormalities (31%); no familial TTP was identified in this series. The schistocytes of peripheral blood smears were present in all cases with a mean frequency of 4.6% (range from 0.3% to 13.4%). Plasma ADAMTS 13 activity was determined in 22 patients with the FRET-vWF86 assay. Only 4 idiopathic TTP patients (18.2%) had severe ADAMTS 13 deficiency (activity<10%); 9 (40.9%) had moderate decrease of ADAMTS 13 activity (activity: 10-40%); another 9 (40.91%) had normal ADAMTS 13 activity (>40%). T lymphocyte subpopulation was measured in 23 TTP patients with FACS Calibur; 14 of the 23 (60.9%) had significantly decreased CD4 cells count and CD4/CD8 ratio, suggesting cellular immune dysfunction may be involved in the pathogenesis of TTP. In the studies, plasmapheresis is the main therapeutic method. 26 of 31 patients (83.9%) accepting plasmapheresis achieved complete remission; those patients who only underwent plasma infusion had low remission rate (18.2%) and high mortality (9/11; 81.8%). Four patients with packed RBC infusion manifested transient exacerbation of neurologic or psychiatric symptoms. In conclusion, the diagnosis of TTP in China is still based on clinical features including evidence of microangiopathic hemolysis. Severe ADAMTS 13 activity deficiency might be a valuable indicator for idiopathic TTP diagnosis. Further studies are needed to determine the real value of ADAMTS 13 activity for TTP diagnosis and whether T lymphocytes subset dysregulation plays important role in TTP pathogenesis.

An intron mutation in the ACVRL1 may be associated with a transcriptional regulation defect in a Chinese family with hereditary hemorrhagic telangiectasia.

PURPOSE: To identify a novel pathogenic gene mutation present in a Chinese family with hereditary hemorrhagic telangiectasia (HHT) and to determine if an intron mutation may influence the transcriptional activity of the ACVRL1 gene. METHODS: HHT family members were ascertained following the presentation of proband and involved subjects. All family members (n = 5) and 113 healthy individuals were genotyped for the variant in intron 6 c.772+27G>C of ACVRL1 gene. The genomic structure of ACVRL1 in affected HHT patients and healthy individuals was determined by long range PCR and sequencing. The expression of ACVRL1 mRNA and protein in patients with HHT was evaluated using real-time polymerase chain reaction and immunoblot analysis. Luciferase activity assay and electrophoretic mobility shift assay (EMSA) were performed to uncover the mechanism of intron-related transcriptional regulation. RESULTS: Only one novel mutation in intron 6 (c.772+27G>C) of ACVRL1 gene, no other mutation, abnormal splice, gross genomic deletion or rearrangement was found in this HHT2 family. Compared with healthy individuals, ACVRL1 mRNA and protein were significantly decreased in affected HHT2 individuals. Luciferase activity assay demonstrated that the transcriptional activity of the mutated ACVRL1 was significantly lower than that of the wild-type of intron 6; EMSA results showed that intron 6 c.772+27G>C mutation was able to inhibit the binding of transcriptional factor Sp1. CONCLUSIONS: A novel intron mutation in ACVRL1 gene is associated with familial HHT2. The mechanisms may be involved in the down-regulation of ACVRL1 gene transcription.

Antithrombin Cambridge II(A384S) mutation frequency and antithrombin activity levels in 120 of deep venous thrombosis and 150 of cerebral infarction patients in a single center in Southern China.

Antithrombin Cambridge II(A384S) mutation shows a relatively high frequency in western population. Some studies suggest that the mutation is an independent genetic risk factor both for deep vein thrombosis (DVT) and for arterial thrombosis, but whether the mutation has racial difference or has a general significance for thrombophilia remains unclear. In this study we performed an analysis of the prevalence of the mutation in Chinese southern population; Also, the antithrombin activity levels were evaluated in each investigated individual. The studies included 120 patients with DVT, 150 patients with cerebral infarction, and 110 controls. The mutation was detected using polymerase chain reaction/PvuII restrictive fragment length polymorphism procedures. Antithrombin activity assay was done using chromogenic substrate method. The results showed that no antithrombin Cambridge II mutation was detected in all three groups (DVT, cerebral infarction and controls), the incidence was 0/380. Plasma antithrombin activity was 91.37% +/- 16.15% in the DVT patients and 102.68% +/- 13.10% in the controls; the antithrombin activity was significantly reduced in the DVT group (P < 0.0001). In DVT patients, eight cases were identified as primary antithrombin deficiency, accounting for an incidence of 6.7%. No significant difference was found for antithrombin activity between cerebral infarction group and controls. These results suggest that antithrombin Cambridge II mutation has a racial difference, and may not be a valuable risk factor of thrombophilia in Asian population, and antithrombin deficiency remains a major genetic risk factor for DVT patients in China.

[The frequency of JAK2 V617F mutation, expression level of phosphorylated JAK/STATs proteins and their clinical significance in myeloproliferative disorders patients].

OBJECTIVE: To investigate the frequency of JAK2 V617F mutation in 145 myeloproliferative disorders (MPDs) patients, analyze the correlation between JAK2 V617F mutation and clinical features. METHODS: The JAK2 V617F mutation was detected by direct DNA sequencing of PCR product and allele-specific PCR respectively. The expression of JAK2, phospho-JAK2 and phospho-STAT5 proteins was determined by Western blot. The clinical data of MPDs patients with or without JAK2 V617F mutation was collected and analyzed for evaluating the clinical significance of JAK2 V617F mutation. RESULTS: 1) The frequency of JAK2 V617F mutation for PV, IMF, ET was 92%, 58%, 50% respectively. Compared with conventional DNA sequencing (PV 84%, IMF 44%, ET 39%, respectively), allele-specific PCR exhibited a higher sensitivity in JAK2 V617F mutation detection. 2) The expression levels of phospho-JAK2 and phospho-STAT5 in peripheral blood mononuclear cells (PBMNCs) were upregulated significantly in JAK2 V617F-positive patients than in JAK2 V617F negative patients. 3) Compared with the patients with no JAK2 V617F mutation, the JAK2 V 617F-positive patients' features were as follows: older age of onset, higher mean leukocyte counts, lower platelet counts and smaller spleen volume. Frequency of thrombosis events in PT, ET, IMF was 17%, 32%, 16% respectively for JAK2 V617F positive group, and 0% (PV), 16% (ET), 5% (IMF) for JAK2 V617F negative group. CONCLUSIONS: MPDs patients display higher frequency of JAK2 V617F mutation. JAK2 V617F mutation positive patients predispose to a thrombosis tendency.

[The dynamic analysis and the clinical significance of vascular endothelial cell markers and hemolysis parameters in thrombotic thrombocytopenic purpura].

OBJECTIVE: To monitor the changes of hemolysis parameters and endothelial cell markers in thrombotic thrombocytopenic purpura (TTP) and reveal the clinical significance of these changes. METHODS: vWF-cleaving protease (vWF-CP) activity in 3 cases of TTP was detected by Western blot. The percentages of fragmented red cells (FRC) were counted throughout the entire clinical course. Levels of plasma thrombomodulin were detected by Western blot combined with density screening in TTP and healthy individuals (n = 3). Concentration of plasma VEGF was measured by enzyme-linked immunosorbent assay in TTP and healthy individuals (n = 9). Fundus fluorescein angiography was performed to search the evidence of microvascular thrombosis in one TTP patient with impaired visual acuity. RESULTS: The lower vWF-CP activity was observed in TTP patients; the percentages of FRC in 3 cases of TTP were 1.65%, 2.50%, 3.32% respectively with an average of 2.49% at the onset of and decreased with the improvement of the disease. The levels of plasma TM and VEGF were significantly elevated in TTP than those in healthy individuals, and related to the severity of TTP. Fundus photography in one TTP patient with impaired visual acuity revealed vascular occlusion in fundus arteriole and venulae. CONCLUSIONS: A decreased vWF-CP activity is in favour of TTP diagnosis. Dynamic monitoring of plasma TM and VEGF as well as percentages of FRC are useful indexes for reflecting the severity and evaluating therapeutic response of TTP. Selective fundus fluorescein angiography is useful for the judgement of microvascular thrombosis in TTP.