Application of CD83 and HSF5 to Identify Antemortem and Postmortem Skin Burns. / 应用CD83和HSF5鉴别生前与死后皮肤烧伤.

OBJECTIVES: To explore the forensic application value of cluster of differentiation 83 (CD83) and heat shock transcription factor 5(HSF5) in identifying antemortem and postmortem skin burns. METHODS: Through reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR), CD83 and HSF5 mRNA levels in the skin tissues of antemortem and postmortem burned mice and human samples were detected quantitatively. RESULTS: Compared with the control group and the postmortem burned group, the mRNA levels of CD83 and HSF5 in antemortem burned mice were higher. The high mRNA expressions of CD83 could be detected 96 h after death, and the mRNA expressions of HSF5 could be observed 72 h after death. Compared with undamaged skin, increased CD83 and HSF5 mRNA levels were detected in 11 out of 15 cases(P<0.05). CONCLUSIONS: CD83 and HSF5 can be used in forensic practice as indicators for vital reaction in antemortem burn identification.

Analysis of the fingerprint profile of bioactive constituents of traditional Chinese medicinal materials derived from animal bile using the HPLC-ELSD and chemometric methods: An application of a reference scaleplate.

Traditional Chinese medicinal materials derived from animal bile are widely applied in clinical therapy for thousands of years in several Southeast Asian countries. Although the constituents are similar, these crude drugs exhibit different pharmacological activities; bile acids are the main bioactive constituent. Depending on the source, the price of these crude drugs differs significantly. Therefore, a reliable fingerprint method is needed to analyze and distinguish these crude drugs with a similar composition. In this milieu, we aimed to establish a fingerprint chromatography method that can separate and detect several bile acids simultaneously. A high-performance liquid chromatography separation method was established with evaporative light scattering detection to detect the analytes. The main bioactive constituents of pig bile, cattle bile, sheep bile, bear bile, and three types of cow bezoar were analyzed using the proposed method. The fingerprint chromatography profile of 35 samples were obtained and analyzed using chemometric methods. Considering the differences among samples, a reference scaleplate method was used in the peak alignment procedure. Unsupervised methods (hierarchical cluster analysis and principle component analysis) and supervised methods (K-nearest neighbor, partial least squares discriminant analysis, support vector machine discriminant analysis, and soft independent modeling of class analogy) were used in the chemometric analysis. The results indicated that the fingerprint chromatograms of the seven crude drugs had fingerprint specificity and that they can be well distinguished. In addition, the reference scaleplate method using the chromatogram of a mixed standard solution is practically applicable for peak alignment in the analysis of samples with a large difference in chromatographic peaks. Overall, 17 bile acids can be separated and detected simultaneously using this method and some frequently used TCMMs derived from animal bile can be distinguished accurately.

[Adverse reactions and countermeasures of drugs for children in China].

In recent years, the clinical medication safety for children has gained wide public concern. Because of the growth and development characteristics of the children and drug usage conditions for children, the adverse reactions of drugs in clinic are more common in children than those in adults. In this paper, the common adverse drug reactions and their causes would be briefly introduced, and some suggestions would be put forward on how to reduce the incidence of adverse drug reactions.

Simultaneous determination of nintedanib and its metabolite by UPLC-MS/MS in rat plasma and its application to a pharmacokinetic study.

To establish a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of concentration of nintedanib and its metabolite BIBF 1202 in rat plasma. The nintedanib and its metabolite and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1 mm×50 mm, 1.7 µm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.30 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z540.3→113.1 for nintedanib, m/z526.3→113.0 for BIBF 1202 and m/z285.3→193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated for 1.0-200 ng/mL for nintedanib and 0.5-100 ng/mL for BIBF 1202 using 100 µL of plasma sample. Total time for each chromatograph was 3.0 min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD) <10.8% and the accuracy values ranged from -11.9% to 10.4%. The method was successfully applied to a pharmacokinetic study of nintedanib and BIBF 1202 in rats after oral administration of nintedanib.

Dopamine D3 receptor-regulated NR2B subunits of N-methyl-d-aspartate receptors in the nucleus accumbens involves in morphine-induced locomotor activity.

AIMS: Dopamine and glutamate receptors are densely expressed in the nucleus accumbens (NAc). Active interactions between these receptors contribute to the development of neuropsychiatric diseases, such as drug addiction and relapse. However, the molecular mechanisms underlying these interactions remain unclear. METHODS: This study established a mouse model of intermittent morphine-induced mouse behavioral sensitization model. Western blot and electrophysiological recording methods were performed to directly identify the affective components of morphine behavioral sensitization. RESULTS: Interval morphine administration could cause significant locomotor sensitization. Hyperlocomotion and behavioral locomotor sensitization were significantly suppressed when ifenprodil (5 mg/kg), a selective NR2B subunit-containing N-methyl-d-aspartate (NMDA) receptor antagonist, or nafadotride (25 µg/kg), a dopamine D3 receptor (D3R)-preferring antagonist, was coadministered with morphine. Western blot analysis showed that morphine behavioral sensitization induced a region-specific increase in phosphorylation of NR2B (pNR2B) and total levels of NR2B (NR2B) expression in the NAc. Systemically administered nafadotride attenuated behavioral locomotor sensitization induced by morphine and significantly reversed the overexpression of pNR2B and NR2B subunit-containing NMDA receptor in the NAc. NMDA receptor-mediated excitatory postsynaptic currents in the NAc were also significantly reduced by nafadotride. CONCLUSIONS: These findings suggest that D3Rs are involved in morphine-induced behavioral locomotor sensitization in mice by regulating the NR2B subunits of NMDA receptors in the NAc.

Genetic diversities of 21 non-CODIS autosomal STRs of a Chinese Tibetan ethnic minority group in Lhasa.

In the present study, we investigated 21 short tandem repeat (STR) loci (D6S474, D12ATA63, D22S1045, D10S1248, D1S1677, D11S4463, D1S1627, D3S4529, D2S441, D6S1017, D4S2408, D19S433, D17S1301, D1GATA113, D18S853, D20S482, D14S1434, D9S1122, D2S1776, D10S1435, D5S2500), which are not included in the Combined DNA Index System and Amelogenin locus in 104 randomly selected healthy autochthonous individuals from the Tibetan ethnic minority group residing in the Lhasa region, Tibet Autonomous Region of China. Allelic frequencies, common forensic statistical parameters, and the Hardy-Weinberg equilibrium in this population were calculated with a modified PowerState V12.xls. A total of 143 alleles were found in the Tibetan group with corresponding allelic frequencies ranging from 0.005 to 0.582. The observed heterozygosity, the expected heterozygosity, the power of discrimination, the power of exclusion, and the polymorphic information content ranged from 0.615 to 0.817, 0.559 to 0.787, 0.727 to 0.926, 0.310 to 0.632, and 0.488 to 0.760, respectively. Chi-square tests of the observed genotype frequencies and expected genotype frequencies in the samples showed no departure from the Hardy-Weinberg equilibrium at all loci except for D5S2500. Our results demonstrate that these 21 STRs are highly polymorphic and suitable for anthropological research, population genetics, and forensic paternity testing and human individual identification in this region, and can enrich Chinese ethnical genetic informational resources.

Gene expression in peripheral blood differs after cardioembolic compared with large-vessel atherosclerotic stroke: biomarkers for the etiology of ischemic stroke.

There are no biomarkers that differentiate cardioembolic from large-vessel atherosclerotic stroke, although the treatments differ for each and approximately 30% of strokes and transient ischemic attacks have undetermined etiologies using current clinical criteria. We aimed to define gene expression profiles in blood that differentiate cardioembolic from large-vessel atherosclerotic stroke. Peripheral blood samples were obtained from healthy controls and acute ischemic stroke patients (<3, 5, and 24 h). RNA was purified, labeled, and applied to Affymetrix Human U133 Plus 2.0 Arrays. Expression profiles in the blood of cardioembolic stroke patients are distinctive from those of large-vessel atherosclerotic stroke patients. Seventy-seven genes differ at least 1.5-fold between them, and a minimum number of 23 genes differentiate the two types of stroke with at least 95.2% specificity and 95.2% sensitivity for each. Genes regulated in large-vessel atherosclerotic stroke are expressed in platelets and monocytes and modulate hemostasis. Genes regulated in cardioembolic stroke are expressed in neutrophils and modulate immune responses to infectious stimuli. This new method can be used to predict whether a stroke of unknown etiology was because of cardioembolism or large-vessel atherosclerosis that would lead to different therapy. These results have wide ranging implications for similar disorders.