Determination of 16 Selected Trace Elements in Children Plasma from China Economical Developed Rural Areas Using High Resolution Magnetic Sector Inductively Coupled Mass Spectrometry

A rapid, accurate, and high performance method of high resolution sector field inductively coupled plasma mass spectrometry (HR-ICP-MS) combined with a small-size sample (0.1 mL) preparation was established. The method was validated and applied for the determination of 16 selected plasma trace elements (Fe, Cu, Zn, Rb, B, Al, Se, Sr, V, Cr, Mn, Co, As, Mo, Cd, and Pb). The linear working ranges were over three intervals, 0-1 g/L, 0-10 g/L and 0-100 g/L. Correlation coefficients (R 2 ) ranged from 0.9957 to 0.9999 and the limits of quantification (LOQ) ranged from 0.02 g/L (Rb) to 1.89 g/L (Se). The trueness (or recovery) spanned from 89.82% (Al) to 119.15% (Se) and precision expressed by the relative standard deviation (RSD %) for intra-day ranging from 1.1% (Zn) to 9.0% (Se), while ranged from 3.7% (Fe) to 12.7% (Al) for interday. A total of 440 plasma samples were collected from Chinese National Nutrition and Health Survey Project 2002 (CNNHS 2002), which represented the status of plasma trace elements for the children aged 3-12 years from China economical developed rural areas. The concentrations of 16 trace elements were summarized and compared by age groups and gender, which can be used as one of the basic components for the formulation of the baseline reference values of trace elements for the children in 2002

MUX64, an analogue 64-to-1 multiplexer ASIC for the ATLAS High Granularity Timing Detector

We present the design and the performance of MUX64, a 64-to-1 analogue multiplexer ASIC for the ATLAS High Granularity Timing Detector (HGTD). The MUX64 transmits one of its 64 inputs selected by six address lines for the voltages or temperatures being monitored to an lpGBT ADC channel. The prototype ASICs fabricated in TSMC 130 nm CMOS technology were prepared in wire-bonding and QFN88 packaging format. A total of 280 chips was examined for functionality and quality assurance. The accelerated aging test conducted at 85 degrees celsius shows negligible degradation over 16 days

Systematic Integration of Brain eQTL and GWAS Identifies ZNF323 as a Novel Schizophrenia Risk Gene and Suggests Recent Positive Selection Based on Compensatory Advantage on Pulmonary Function

Genome-wide association studies have identified multiple risk variants and loci that show robust association with schizophrenia. Nevertheless, it remains unclear how these variants confer risk to schizophrenia. In addition, the driving force that maintains the schizophrenia risk variants in human gene pool is poorly understood. To investigate whether expression-associated genetic variants contribute to schizophrenia susceptibility, we systematically integrated brain expression quantitative trait loci and genome-wide association data of schizophrenia using Sherlock, a Bayesian statistical framework. Our analyses identified ZNF323 as a schizophrenia risk gene (P = 2.22×10-6). Subsequent analyses confirmed the association of the ZNF323 and its expression-associated single nucleotide polymorphism rs1150711 in independent samples (gene-expression: P = 1.40×10-6; single-marker meta-analysis in the combined discovery and replication sample comprising 44123 individuals: P = 6.85×10−10). We found that the ZNF323 was significantly downregulated in hippocampus and frontal cortex of schizophrenia patients (P = .0038 and P = .0233, respectively). Evidence for pleiotropic effects was detected (association of rs1150711 with lung function and gene expression of ZNF323 in lung: P = 6.62×10-5 and P = 9.00×10-5, respectively) with the risk allele (T allele) for schizophrenia acting as protective allele for lung function. Subsequent population genetics analyses suggest that the risk allele (T) of rs1150711 might have undergone recent positive selection in human population. Our findings suggest that the ZNF323 is a schizophrenia susceptibility gene whose expression may influence schizophrenia risk. Our study also illustrates a possible mechanism for maintaining schizophrenia risk variants in the human gene poo

A General Model for Multilocus Epistatic Interactions in Case-Control Studies

Background: Epistasis, i.e., the interaction of alleles at different loci, is thought to play a central role in the formation and progression of complex diseases. The complexity of disease expression should arise from a complex network of epistatic interactions involving multiple genes. Methodology: We develop a general model for testing high-order epistatic interactions for a complex disease in a casecontrol study. We incorporate the quantitative genetic theory of high-order epistasis into the setting of cases and controls sampled from a natural population. The new model allows the identification and testing of epistasis and its various genetic components. Conclusions: Simulation studies were used to examine the power and false positive rates of the model under different sampling strategies. The model was used to detect epistasis in a case-control study of inflammatory bowel disease, in which five SNPs at a candidate gene were typed, leading to the identification of a significant three-locus epistasis

Pharmacokinetics and metabolism of icaritin in rats by UPLC‐MS/MS

Icaritin (ICT) has distinct bioactivities, especially known for its beneficial effects on bone-related degenerative disorders; however, its pharmacokinetic properties remain unknown. A novel developed UPLC-MS/MS method for the determination of ICT and its main metabolite glucuronidated icaritin (GICT) was firstly applied to pharmacokinetic and metabolism studies of ICT in female rats, which were intraperitoneally given 40 mg/kg ICT. Following the protein precipitation of plasma samples with acetonitrile, ICT and GICT were separated on a C18 column using gradient elution mode and quantified in the multiple reaction monitoring mode. The linearities were acceptable for ICT (r = 0.9960) and GICT (r = 0.9968), and the lower limit of quantification values was 0.5 and 5 ng/ml, respectively. The accuracy fell in the range of 92.0%–103.1% and precisions were within 9.5%. Good linearity, accuracy, precision, and recovery were achieved for the UPLC-MS/MS method. ICT was predominantly and rapidly biotransformed to GICT which was slowly eliminated in vivo with a terminal half-life value of 4.51 hr. Pharmacokinetics of pure ICT eliminated biotransformation interference of Epimedium extract and disclosed genuine pharmacokinetic manner of ICT, as well as firstly elucidated low concentration and bioavailability of ICT in rat plasma

Pharmacokinetics and metabolism of icaritin in rats by UPLC-MS/MS

Icaritin (ICT) has distinct bioactivities, especially known for its beneficial effects on bone-related degenerative disorders; however, its pharmacokinetic properties remain unknown. A novel developed UPLC-MS/MS method for the determination of ICT and its main metabolite glucuronidated icaritin (GICT) was firstly applied to pharmacokinetic and metabolism studies of ICT in female rats, which were intraperitoneally given 40 mg/kg ICT. Following the protein precipitation of plasma samples with acetonitrile, ICT and GICT were separated on a C18 column using gradient elution mode and quantified in the multiple reaction monitoring mode. The linearities were acceptable for ICT (r = 0.9960) and GICT (r = 0.9968), and the lower limit of quantification values was 0.5 and 5 ng/ml, respectively. The accuracy fell in the range of 92.0%–103.1% and precisions were within 9.5%. Good linearity, accuracy, precision, and recovery were achieved for the UPLC-MS/MS method. ICT was predominantly and rapidly biotransformed to GICT which was slowly eliminated in vivo with a terminal half-life value of 4.51 hr. Pharmacokinetics of pure ICT eliminated biotransformation interference of Epimedium extract and disclosed genuine pharmacokinetic manner of ICT, as well as firstly elucidated low concentration and bioavailability of ICT in rat plasma

Clinical Observation of Erlotinib as the First-line Treatment for Patients with Advanced Non-small Cell Lung Cancer

Background and objective To evaluate the efficacy and toxicity of erlotinib as the first-line therapy for advanced non-small cell lung cancer (NSCLC). Methods A total of 28 pathologically-confirmed NSCLC patients who could not receive willingly or tolerate traditional cytotoxic drugs chemotherapy were enrolled. Erlotinib was orally administered 150 mg daily until disease progression or the occurrence of intolerable toxicity. Results Among a total of 28 patients, the objective response rate (ORR) of erlotinib was 28.6%. The disease control rate (DCR) was 60.7%. The rate of symptom relief was 53.6%. The median progression free survival (PFS) was 3.2 (95%CI: 0.851-5.585) months. The median overall survival (OS) was 9.6 (95%CI: 7.179-12.021) months. One-year survival rate was 32.1%. The therapeutic effect was better in patients with rash. Most of the toxicities were grade I and grade II toxicity. The most common adverse events were rash (46.4%), diarrhea (32.1%), skin dry (25.0%), anorexia(17.9%), fatigue (10.7%) and increased transaminase (7.1%). Conclusion Erlotinib provided another choice for the patients who could not willingly receive or tolerate chemotherapy