The Role of Format Familiarity and Word Frequency in Chinese Reading.

For Chinese readers, reading from left to right is the norm, while reading from right to left is unfamiliar. This study comprises two experiments investigating how format familiarity and word frequency affect reading by Chinese people. Experiment 1 examines the roles of format familiarity (reading from left to right is the familiar Chinese format, and reading from right to left is the unfamiliar Chinese format) and word frequency in vocabulary recognition. Forty students read the same Chinese sentences from left to right and from right to left. Target words were divided into high and low frequency words. In Experiment 2, participants engaged in right-to-left reading training for 10 days to test whether their right-to-left reading performance could be improved. The study yields several main findings. First, format familiarity affects vocabulary recognition. Participants reading from left to right had shorter fixation times, higher skipping rates, and viewing positions closer to word center.. Second, word frequency affects vocabulary recognition in Chinese reading. Third, right-to-left reading training could improve reading performance. In the early indexes, the interaction effect of format familiarity and word frequency was significant. There was also a significant word-frequency effect from left to right but not from right to left. Therefore, word segmentation and vocabulary recognition may be sequential in Chinese reading.

Evaluation of the inhibition effects of apatinib on human and rat cytochrome P450.

Apatinib, a small molecule anti-angiogenic drug, is proven to be safe and effective for treatment of advanced gastric cancer (AGC). It is also a single drug that significantly prolongs survival after failure of standard chemotherapy for AGC, which has attracted the research interest. The purpose of this study is to evaluate the inhibition effects of apatinib on human and rat cytochrome P450, including CYP3A2/4, CYP2B1/6, CYP2C9/11, CYP2D1/6, and CYP2E1. The IC50 and IC50-shift results indicated that apatinib might not be a time-dependent inhibitor. Apatinib was a weak inhibitor of human CYP2E1 (IC50>10 µM) but inhibited CYP2B6/2B1 and CYP2D6/2D1 in a competitive way (Ki = 3.84/0.59 and 5.41/0.87 µM), and inhibited CYP3A4/3A2 and rat CYP2E1 in a mixed way (Ki = 11.50/1.83 and 13.06 µM). On CYP2C9, apatinb exhibited the noncompetitive inhibition (Ki = 0.71 µM) while it inhibited CYP2C11 uncompetitively (Ki = 3.30 µM).

Fabrication of Bi­Sb­Te Thermoelectric by Cold-Pressed Sintering for Motorcycle Exhaust.

This study was conducted on the Bi­Sb­Te thermoelectric material which is cold-pressed Sintering under 750 Mpa to make square thermoelectric pairs with size 8.2 mm × 8.2 mm and thicknesses 0.8 mm and 1.5 mm. The zone melting method was used to acquire P-type thermoelectric material Bi0.4Sb1.6Te3 and N-type thermoelectric material Bi2Te2.5Se0.5. At temperature 383 K, the measured Seebeck coefficient of Bi0.4Sb1.6Te3 is 222 µV/K, and its thermoelectric figure of merit ZT is 1.35. At temperature 400 K, the measured Seebeck coefficient of Bi2Te2.5Se0.5 is 210 µV/K, and its thermoelectric figure of merit ZT is 1.13. Using Solder paste Sn42Bi58 and copper electrode plate are in series connection with 16 pieces of P/N thermoelectric material to form thermoelectric modules. The thermoelectric module is actually pasted on the motorcycle waste heat source to be evaluated the performance, making the cold-end temperature dissipation heat can enhance the temperature difference between it so as to increase the output power. Increasing the leg thickness of thermoelectric module and making the about 35 °C temperature-difference of those can obviously enhance the performance of in terms of its voltage, its thermoelectric figure of merit ZT and output power of the thermoelectric modules.

Risk and association of HLA with oxcarbazepine-induced cutaneous adverse reactions in Asians.

OBJECTIVE: To investigate the risk and genetic association of oxcarbazepine-induced cutaneous adverse reactions (OXC-cADRs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), in Asian populations (Chinese and Thai). METHODS: We prospectively enrolled patients with OXC-cADRs in Taiwan and Thailand from 2006 to 2014, and analyzed the clinical course, latent period, drug dosage, organ involvement, complications, and mortality. We also investigated the carrier rate of HLA-B*15:02 and HLA-A*31:01 of patients with OXC-cADRs and compared to OXC-tolerant controls. The incidence of OXC-SJS/TEN was compared with carbamazepine (CBZ)-induced SJS/TEN according to the nationwide population dataset from the Taiwan National Health Insurance Research Database. RESULTS: We enrolled 50 patients with OXC-cADRs, including 20 OXC-SJS/TEN and 6 drug reaction with eosinophilia and systemic symptoms, of Chinese patients from Taiwan and Thai patients from Thailand. OXC-cADRs presented with less clinical severity including limited skin detachment (all ≦5%) and no mortality. There was a significant association between HLA-B*15:02 and OXC-SJS (p = 1.87 × 10-10; odds ratio 27.90; 95% confidence interval [CI] 7.84-99.23) in Chinese and this significant association was also observed in Thai patients. The positive and negative predictive values of HLA-B*15:02 for OXC-SJS/TEN were 0.73% and 99.97%, respectively. HLA-A*31:01 was not associated with OXC-cADRs. The incidence and mortality of OXC-SJS/TEN was lower than CBZ-STS/TEN in new users (p = 0.003; relative risk 0.212; 95% CI 0.077-0.584). CONCLUSIONS: Our findings suggest that HLA-B*15:02 is significantly associated with OXC-SJS in Asian populations (Chinese and Thai). However, the severity and incidence of OXC-SJS/TEN are less than that of CBZ-SJS/TEN. The need for preemptive HLA-B*15:02 screening should be evaluated further.

Genetic variants associated with phenytoin-related severe cutaneous adverse reactions.

IMPORTANCE: The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown. OBJECTIVE: To investigate the genetic factors associated with phenytoin-related severe cutaneous adverse reactions. DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia. MAIN OUTCOMES AND MEASURES: Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions. RESULTS: The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 (CYP2C9*3) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P=1.1 × 10(-17)). The statistically significant association between CYP2C9*3 and phenytoin-related severe cutaneous adverse reactions was observed in additional samples from Taiwan, Japan, and Malaysia. A meta-analysis using the data from the 3 populations showed an overall odds ratio of 11 (95% CI, 6.2-18; z=8.58; P < .00001) for CYP2C9*3 association with phenytoin-related severe cutaneous adverse reactions. Delayed clearance of plasma phenytoin was detected in patients with severe cutaneous adverse reactions, especially CYP2C9*3 carriers, providing a functional link of the associated variants to the disease. CONCLUSIONS AND RELEVANCE: This study identified CYP2C variants, including CYP2C9*3, known to reduce drug clearance, as important genetic factors associated with phenytoin-related severe cutaneous adverse reactions.

Genotype-phenotype association between HLA and carbamazepine-induced hypersensitivity reactions: strength and clinical correlations.

BACKGROUND: Increasing studies reported genetic susceptibility to drug hypersensitivity reactions, as exemplified by the HLA-A*31:01 and HLA-B*15:02 association with carbamazepine (CBZ)-induced hypersensitivity reactions, such as maculopapular exanthema (MPE), drug rash with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). OBJECTIVE: To carry out a comprehensive analysis on the clinical spectrum and HLA genotype-phenotype correlations in CBZ-induced hypersensitivity reactions. METHODS: We analyzed the clinical information of 194 patients with CBZ hypersensitivity (51 MPE, 23 DRESS, 112 SJS/TEN, and 8 cases with other phenotypes), and 152 CBZ-tolerant controls. All are Han Chinese. We examined the HLA-A/HLA-B genotypes, gene dosage, and drug dosage effects. RESULTS: CBZ-SJS/TEN showed the strongest association with the HLA-B*15:02 allele (Pc=5.8×10(-43); odds ratio (OR) (95% CI)=97.6(42.0-226.8)), in which HLA-B*15:02 was identified in all patients (25/25) with SJS/TEN with >5% body surface area (BSA) skin detachment, but lost its 100% association (85.1%, 74/87) in SJS with <5% BSA detachment. In contrast, HLA-B*40:01 showed negative association with CBZ-induced SJS/TEN ((Pc=8.3×10(-5); OR (95% CI)=0.22(0.1-0.4)). By comparison, CBZ-induced MPE/DRESS had no association with HLA-B*15:02, but linked to HLA-A*31:01 (Pc=2.7×10(-3); OR (95% CI)=6.86(2.4-19.9), and HLA-B*51:01 (Pc=0.01; OR (95% CI)=4.56(2.0-10.5)). No gene dosage or CBZ dosage effects was observed. CONCLUSION: This study reported the different strength of HLA association with CBZ hypersensitivity in Han Chinese. With the increasing application of pharmacogenetic markers, the HLA genotype-phenotype correlations and the results of the test need to be carefully interpreted for CBZ-induced hypersensitivity reactions.

Synthesis and in vitro antifungal evaluation of 1,3,5-trisubstituted-2-pyrazoline derivatives.

Pyrazolines, the well-known five-membered nitrogen-containing heterocyclic compounds, have received considerable interests in the fields of medicinal and agricultural chemistry because of their broad spectrum of biological activities. To discover more potent antifungal compounds, a series of structurally related 1,3,5-trisubstituted-2-pyrazoline derivatives have been synthesized by introducing furan rings regarded as bioactive substructure into the scaffold of pyrazolines and tested for their activities against six plant pathogenic fungi in vitro. The preliminary bioassays indicated that almost all synthesized compounds had displayed variable growth inhibitory effects on the tested pathogenic fungi. In particular, compounds 4, 7, 9, 12, 18, 19, and 38 displayed excellent antifungal activities against Rhizoctonia solani and their inhibition of growth reached 100% at the concentration of 20 mg/L. Additionally, compounds 9 and 19 bearing two furan rings, respectively, at site 3 and site 5 of the pyrazoline cycle showed the strongest activities against R. solani (the EC(50) were 3.46 mg/L and 3.20 mg/L). The bioactivity results provide good starting templates for further structural optimization of pyrazoline derivatives.

Cutaneous intravascular NK-cell lymphoma: report of a rare variant associated with Epstein-Barr virus.

Intravascular lymphoma (IVL) is a rare variant of non-Hodgkin lymphoma with a predilection for skin and brain. Except a few cases of T-cell lineage, most of the reported cases were large B-cell lymphomas. We encountered a case of cutaneous IVL in a 71-year-old woman presenting with multiple erythematous patches and nodules on her trunk and extremities. The intravascular large cells showed an immunophenotype of CD3epsilon(+);, CD5(-), CD20(-), CD30(-), CD56(+), and TIA-1(+). The lymphoma cells were also positive for Epstein-Barr virus by Epstein-Barr virus-encoded RNA in situ hybridization test and the T-cell receptor gene was germline. This IVL differs from nasal type NK/T-cell lymphoma only by its intravascular nature. Only 3 cases of intravascular NK-cell lymphoma have been reported before. Because this variant is extremely rare, our case is documented and compared with the 3 previously reported cases.

HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol.

Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a frequent cause of severe cutaneous adverse reactions (SCAR), which include the drug hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The adverse events are unpredictable and carry significant morbidity and mortality. To identify genetic markers for allopurinol-SCAR, we carried out a case-control association study. We enrolled 51 patients with allopurinol-SCAR and 228 control individuals (135 allopurinol-tolerant subjects and 93 healthy subjects from the general population), and genotyped for 823 SNPs in genes related to drug metabolism and immune response. The initial screen revealed strong association between allopurinol-SCAR and SNPs in the MHC region, including BAT3 (encoding HLA-B associated transcript 3), MSH5 (mutS homolog 5), and MICB (MHC class I polypeptide-related sequence B) (P < 10(-7)). We then determined the alleles of HLA loci A, B, C, and DRB1. The HLA-B*5801 allele was present in all (100%) 51 patients with allopurinol-SCAR, but only in 20 (15%) of 135 tolerant patients [odds ratio 580.3 (95% confidence interval, 34.4-9780.9); corrected P value = 4.7 x 10(-24)] and in 19 (20%) of 93 of healthy subjects [393.51 (23.23-6665.26); corrected P value = 8.1 x 10(-18)]. HLA alleles A*3303, Cw*0302, and DRB1*0301 were in linkage disequilibrium and formed an extended haplotype with HLA-B*5801. Our results indicated that allopurinol-SCAR is strongly associated with a genetic predisposition in Han Chinese. In particular, HLA-B*5801 allele is an important genetic risk factor for this life-threatening condition.

Urticarial vasculitis and dermatomyositis in a patient with nasopharyngeal carcinoma.

Urticarial vasculitis has rarely been described in association with polymyositis. We report the case of a 37-year-old man with dermatomyositis and nasopharyngeal carcinoma who presented initially with urticarial vasculitis. The lesions of urticarial vasculitis were initially photodistributed, indicating photosensitivity. The patient was treated with systemic steroids, chemotherapy (cisplatin and fluorouracil), and radiation therapy. The tumor and urticarial vasculitis completely resolved, and the myositis improved.