[The mechanism, prevention and diagnosis of cutaneous adverse drug reaction].

Adverse drug reactions are often encountered in the process of medication and are quite troublesome for clinicians. Skin is one of the most frequently affected organs by adverse drug reactions. Adverse drug reactions involving skin are called "drug-induced dermatitis" or "drug eruption". In some rare instances, drug eruption can be severe and life-threatening which is known as severe cutaneous adverse drug reaction. However, due to the mixed use of drugs, it is difficult to identify the culprit drug, which makes multiple drugs needed to be avoided. Recently, many studies have found that HLA alleles are closely related to the certain culprit drug. HLA genotyping before administration can significantly reduce the incidence of severe cutaneous adverse drug reaction related to certain drugs. Since limited HLA alleles are found, HLA genotyping can only prevent adverse drug reaction to a limited extent. At present, drug provocation tests are regarded as the "gold standard" to identify the culprit drug. However, this diagnostic program has not been widely developed because of the high risk. In addition, a variety of in vivo and in vitro diagnostic methods (including drug patch test, drug skin test, drug specific IgE test, basophil activation test, lymphocyte transformation test, et al) also provide evidences to identify the culprit drug.

[Clinical and pathological differences between papillary thyroid carcinoma with Graves' disease and papillary thyroid carcinoma with Hashimoto's thyroiditis].

Objective: To explore the clinical and pathological differences between papillary thyroid carcinoma (PTC) with Graves' disease (GD) and PTC with Hashimoto's thyroiditis (HT). Methods: A total of 33 PTC patients with GD and 132 PTC patients with HT in the First Affiliated Hospital of China Medical University from January 2009 to December 2015 were enrolled. The clinical and histopathological data were analyzed. Results: The average serum concentration of thyroid stimulating hormone (TSH) of PTCs with GD was significantly lower than PTCs with HT [0.01 (0, 0.10) mU/L vs 2.28(1.51, 3.14) mU/L, P<0.001]. However, there was no significant difference between the two groups in nodule diameter [(15.7±7.0) mm vs (13.5±7.8)mm, P=0.14], percentage of lymph node metastasis (LNM) [33.3%(11/33) vs 39.4%(52/132), P=0.52], TNM stage Ⅲ-Ⅳ disease [12.1%(4/33) vs 11.4% (15/132), P=1.00], papillary thyroid micro-carcinoma (PTMC) [60.6% (20/33) vs 60.6%(80/132), P=1.00]and classic PTC in all its variant patterns [81.8%(27/33) vs 75.0%(99/132), P=0.36]. The age (P<0.01, OR=0.95, 95%CI: 0.92-0.98) and PTMC (P<0.01, OR=0.30, 95%CI: 0.13-0.67), rather than TSH (P=0.08) were independently correlated with LNM. Recurrence rate of PTC with GD was significantly lower than PTC with HT (log-rank test, P=0.03). In Cox proportional hazards regression model, variant pattern of PTC was independently correlated with recurrence rate (P<0.05). Conclusions: GD with PTC wasn't different from HT concomitant with PTC, except for thyroid function test. In addition, recurrence rate of PTC with GD was lower than that of PTC with HT after controlling TSH in the same level.

CpG methylation of dmrt1 and cyp19a promoters in relation to their sexual dimorphic expression in the Japanese flounder Paralichthys olivaceus.

To better understand the effects of DNA methylation on the expression patterns of dmrt1 (Doublesex and Mab-3-related transcription factor 1) and cyp19a (Cytochrome P450 19a) in the Japanese flounder Paralichthys olivaceus, quantitative expressions, cellular distributions and cytosine-p-guanine (CpG) methylation patterns of these two genes in the gonads were analysed. The results showed that P. olivaceus dmrt1 expression was 70 times higher in the testis than in the ovary (P < 0·05). Its mRNA was detected clearly in spermatocytes and Sertoli cells of the testis, but weakly in the ovary. Paralichthys olivaceus cyp19a expression was 40 times higher in the ovary than in the testis (P < 0·01). Its mRNA was detected clearly in follicular cells of the ovary, but weakly in spermatocytes of the testis. The dmrt1 promoter CpGs were not methylated in the testis, whereas 57·69% were methylated in the ovary. For the cyp19a promoter CpGs, 97·5% were methylated in the testis and 73·33% were methylated in the ovary. These findings demonstrate that P. olivaceus dmrt1 and cyp19a are sex-related genes with sexual dimorphic expression, CpG methylation levels of the two genes are consistent with their expression quantities, and this epigenetic modification can influence the differential expression of genes in the gonads of P. olivaceus.

Isolation and characterization of novel microsatellite loci in Nibea albiflora.

Eleven novel microsatellite loci were isolated from a (CA)10-enriched genomic DNA library of Nibea albiflora. The characteristics of these microsatellites were determined in a sample of 48 N. albiflora individuals. The number of alleles at the 11 microsatellite loci ranged from 5 to 25, with an average of 13.5 per locus. The observed and expected heterozygosities varied from 0.583 to 0.917 and from 0.568 to 0.964, respectively. Eight of the 11 microsatellite loci conformed to the Hardy-Weinberg equilibrium. No significant linkage disequilibrium was found among all 11 loci. These polymorphic microsatellites will be useful for population genetic analyses of N. albiflora.

Development and characterization of novel microsatellite markers in the rock bream fish Oplegnathus fasciatus.

The rock bream fish Oplegnathus fasciatus is one of the most popular aquaculture species in China. In the present study, 15 novel polymorphic microsatellite loci were isolated and characterized from a wild population of O. fasciatus from the Zhoushan coast of China. The number of alleles per polymorphic locus ranged from 4 to 9 in a sample of 30 individuals. Observed and expected heterozygosities per locus varied from 0.267 to 0.767 and from 0.395 to 0.859, respectively. Eleven of the 15 microsatellite loci conformed to Hardy-Weinberg equilibrium. No significant linkage disequilibrium between pairs of loci was detected. The present microsatellite markers could provide a useful tool for the genetic analyses of O. fasciatus.

rDNA ITS sequences among morphotypes of Keratell cochlearis, Keratell quadrata and Brachionus forficula (Rotifera).

Morphological variation in rotifers is affected by environmental conditions, making it hard to identify some rotifer taxa. We examined the rDNA ITS sequences of 10 unspined (KCU1-KCU10) and 17 spined (KCS1-KCS17) Keratell cochlearis clones, 26 two-spined (KQT1-KQT26), 18 single-spined (KQS1-KQS18) and 9 unspined (KQU1-KQU9) K. quadrata clones, and 17 long-spined (BL1-BL17) and 11 short-spined (BS1-BS11) Brachionus forficula clones collected from Lake Tingtang in Wuhu city, China. Molecular phylogenetic trees were constructed by neighbor-joining, maximum-likelihood, maximum parsimony, and Bayesian inference methods using B. calyciflorus as an outgroup. The K. cochlearis clones included 20 haplotypes, the K. quadrata clones included 37 haplotypes, and the B. forficula clones included 25 haplotypes. Different morphotypes of each rotifer species had shared haplotypes. Sequence divergences were 0.1-8.9% among different K. cochlearis haplotypes, and 8.1-8.9% between KCHAP1 (KCU1 and KCU10), KCU3, KCU4 and KCU6, and the other haplotypes. Sequence divergences were 0.1-14.5% among different K. quadrata haplotypes, and 11.9-14.5% between KQS17 and the other haplotypes. Sequence divergences were 0.1-11.7% among different B. forficula haplotypes, 11.0-11.7% between BL15 and the other haplotypes, 9.3-10.1% between BS3 and the other haplotypes, and 11.7% between BL15 and BS3. The four phylogenetic trees all supported that KCHAP1, KCU3, KCU4, KCU6 and the other 16 haplotypes among the 20 K. cochlearis haplotypes, KQS17 and the other 36 haplotypes among the 37 K. quadrata haplotypes, and BL15, BS3 and the other 23 haplotypes among the 25 B. forficula haplotypes all belonged to their own isolated clades. The morphological variation of the three rotifer species was attributed mainly to phenotypic plasticity.

Individual and combined effects of methamphetamine and ketamine on conditioned place preference and NR1 receptor phosphorylation in rats.

Methamphetamine (MA), a commonly abused psychostimulant, induces the drug dependence by enhancing the dopamine-mediated neurotransmission. Ketamine (KET) is a non-competitive N-methyl-D-aspartate receptor antagonist, which can be actually mixed with MA for polydrug abuse. In the present study, the individual and combined effects of KET (10 mg/kg, i.p.) and MA (1 mg/kg, i.p.) on conditioned place preference in rats were investigated. The alterations of serine 897 phosphorylations of NR1 receptors in the striatum and ventral tegmental area of after-conditioning rats were measured immunochemically. The results showed repeated administrations of MA, KET and their combination, at the doses studied, all could induce psychological dependences evaluated by conditioned place preference. KET was not able to suppress the MA-induced place preference. The modulations of NR1 phosphorylations in basal ganglia were partly responsible to place preference. Although the alterations induced by KET were not significant in most areas we studied, MA showed a significant increase in the ventral tegmental area but a marked decrease in caudate putamen and nucleus accumbens. Such alterations were much more significant when KET and MA were combined. These results have important implications for public awareness of harm with combined drug abuse. Further investigations toward the specific interaction of the two drugs are necessary.

The effect of 1,3-diaryl-[1H]-pyrazole-4-acetamides on glucose utilization in ob/ob mice.

This article provides evidence of a new class of compounds, 1,3-diaryl-[1H]-pyrazole-4-acetamides, initially identified from their ability to increase glucose transport in an adipocyte and muscle cell line and ultimately demonstrating dramatic glucose lowering in ob/ob mice, a diabetic animal model. The lead compound, 1, possessed some behavioral-like effects which were removed by structural variation during the course of this investigation. Specifically, 11g (R1 = meta-CF(3), Ar2 = 4'biphenyl, R3 = diethylamide) illustrated the potency of this series with ED(50) values for glucose lowering in ob/ob mice of 3.0 mg/kg/day. Concomitant with its effect on glucose lowering, 11g also caused a 50% reduction in insulin levels consistent with an agent that increases whole body insulin sensitivity. 11g showed favorable pharmacokinetic data with acceptable absorption, negligible metabolism, and good duration of action. 11g demonstrated no appreciable adipogenic effect through PPAR gamma agonism, a characteristic of the thiazolidinediones (TZD), and so represents a potentially new class of agents for the treatment of diabetes.

Total syntheses of bengamides B and E.

Total syntheses of the cytotoxic marine natural products bengamides B and E are described. Both bengamides are prepared via amide coupling of a protected polyhydroxylated lactone intermediate 9 with a suitably substituted aminocaprolactam intermediate. Lactone 9 is prepared in five steps from commercially available alpha-D-glucoheptonic gamma-lactone. The key reactions are a selective deprotection of a 1,2-acetonide in the presence of a 1,3-acetonide and an (E)-selective olefination of an unstable aldehyde using a gem-dichromium reagent. The bengamide B lactam intermediate 10 is prepared in seven steps from commercially available (5R)-5-hydroxy-L-lysine (12). The desired S-configuration at the gamma-OH lactam position is established using the Mitsunobu reaction.

In vivo DNA-protein interactions at hypersensitive site 3.5 of the human beta-globin locus control region.

Using ligation-mediated polymerase chain reaction and in vivo footprinting methods to study the status of DNA-protein interactions at hypersensitive site 3.5 (HS3.5) of the locus control region in K562 and HEL cells, we found that there was protein occupancy in vivo at HS3.5 in both cell lines and the status of DNA-protein interaction was different between K562 and HEL. These data provide direct evidence that specific nuclear factor-DNA complexes form in vivo at functionally important sequence motifs of the HS3.5 in erythroid cells. This indicates that HS3.5 may play an important role in the regulation of the beta-globin gene cluster. K562 is a human erythroleukemia cell line in which the embryonic epsilon-globin gene is predominantly expressed, while the HEL cell line expresses predominantly the fetal beta-globin genes. Thus, HS3.5 might also be involved in the regulation of developmental stage-specific expression of beta-globin genes. Our results are also consistent with the model that each hypersensitive site acts as a functional unit and HS3.5 may facilitate the formation of the HS3 functional unit.

Both locus control region and proximal regulatory elements direct the developmental regulation of beta-globin gene cluster.

Using ligation-mediated PCR and in vivo footprinting methods to study the status of DNA-protein interaction at hypersensitive site 2 of locus control region and beta(maj) promoter of erythroid cells of fetal liver and adult bone marrow, we found that during different developmental periods, the status of DNA-protein interaction at both hypersensitive site 2 and beta(maj) promoter changed significantly, and indicated that locus control region might function through a looping mechanism to regulate the expression of downstream genes, and that distal regulatory elements (locus control region, hypersensitive sites) as well as proximal regulatory elements (promoter, enhancer) of beta-globin gene cluster participate in the regulation of developmental specificity.

Transcatheter double-blade valvotomy for the treatment of valvar pulmonary stenosis.

A transcatheter double-blade valvotome for cutting a stenotic pulmonary valve has been devised. The valvotome consists of a retractable rhomboid structure at its tip, with a blade on each side of its proximal half. By tugging the extended blades from the pulmonary artery to the right ventricle it is possible to tear the stenotic valve. After animal experiments proved the feasibility and safety of this method, it was used in three children with pulmonary stenosis. The results were encouraging.

A case-control study of dietary and nondietary risk factors for breast cancer in Shanghai.

A case-control study of breast cancer (186 cases, 186 population, and 186 hospital controls) was conducted in Shanghai, China, between 1982 and 1984. This population has a high daily caloric intake (population control mean, 2394 kcal) and low percentage of calories from fat (22.7%) compared to Western populations. Cases have a significantly greater daily caloric intake than controls, primarily because of increased consumption of monounsaturated fat for which the relative risk is 1.89 for the highest compared to the lowest quintile (P = 0.02). This finding requires cautious interpretation but seems worthy of further study in populations with similar dietary practices.