A multicenter prospective study of next-generation sequencing-based newborn screening for monogenic genetic diseases in China.

BACKGROUND: Newborn screening (NBS) is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases. The development of next-generation sequencing (NGS) technology provides new opportunities to expand current newborn screening methodologies. METHODS: We designed a a newborn genetic screening (NBGS) panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS. With this panel, a large-scale, multicenter, prospective multidisease analysis was conducted on dried blood spot (DBS) profiles from 21,442 neonates nationwide. RESULTS: We presented the positive detection rate and carrier frequency of diseases and related variants in different regions; and 168 (0.78%) positive cases were detected. Glucose-6-Phosphate Dehydrogenase deficiency (G6PDD) and phenylketonuria (PKU) had higher prevalence rates, which were significantly different in different regions. The positive detection of G6PD variants was quite common in south China, whereas PAH variants were most commonly identified in north China. In addition, NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants, which were normal in conventional NBS, but were confirmed later as abnormal in repeated biochemical testing after recall. Eighty percent of high-frequency gene carriers and 60% of high-frequency variant carriers had obvious regional differences. On the premise that there was no significant difference in birth weight and gestational age, the biochemical indicators of SLC22A5 c.1400C > G and ACADSB c.1165A > G carriers were significantly different from those of non-carriers. CONCLUSIONS: We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS methods. Our data also showed that the prevalence of diseases has significant regional characteristics, which provides a theoretical basis for screening diseases in different regions.

[Research progress of serum pharmacochemistry of traditional Chinese medicine].

Serum pharmacochemistry of traditional Chinese medicine(TCM) is an effective method to rapidly screen the effective substances and reveal the compatibility law of compound by identification and analysis of constituents migrating to blood after oral administration. In the last two decades, it has been universally accepted and widely applied in the field. With the cross-fusion with other disciplines, such as serum pharmacology, pharmacokinetics, metabolomics, network pharmacology and systems biology, serum pharmacochemistry shows comprehensive superiority in explaining drug changes in vivo and in vitro, interactions between drugs, interactions between drug and body, which coincides with the complexity of TCM compatibility, multi-components, multi-targets and multi-mechanisms. Based on the references related with the serum pharmacochemistry from CNKI scholar and Pubmed in 2013-2016, the research results of serum pharmacochemistry were statistically analyzed, and the key technical problems during the study of serum pharmacochemistry, for example, preparation of test sample, selection of experimental animal, determination of drug delivery scheme, method and time of the adoption blood, preparation and pretreatment of blood sample, as well as analysis of constituents migrating to blood, and the solving ways were empirically introduced. In addition, the development and comprehensive application of serum pharmacochemistry in TCM were summarized in this paper, hoping to lay a foundation for the further application of this method in TCM research.