Age and sex specific reference intervals of 13 hematological analytes in Chinese children and adolescents aged from 28 days up to 20 years: the PRINCE study.

OBJECTIVES: Pediatric Reference Intervals in China (PRINCE) is a nationwide initiative that aims to establish and validate harmonized reference intervals (RIs) for Chinese children and adolescents, in which 15,150 healthy volunteers aged up to 20 years were recruited from 11 centers to establish RIs and 7,557 children and adolescents were enrolled from 21 centers to validate RIs. METHODS: The complete blood cell counts (CBC) of venous whole blood were measured by hematology analyzers through Sysmex systems in different centers. Age- and sex-specific RIs were calculated according to the guidelines. RESULTS: Unlike adults with certain levels of analyte concentrations, hematological parameters of children changed through growth and development. Red blood cell counts, hemoglobin, and hematocrit increased with age, and revealed higher concentrations in boys than girls after puberty. White blood cell counts and platelet counts showed significant higher levels than adults before 2 years of age, and then gradually decreased without distinct sex differences. In addition, lymphocyte counts decreased with age while neutrophil counts showed an opposite trend. The lower and upper limits of pediatric RIs of CBC were different from those of adults. CONCLUSIONS: The validation of RIs indicated that the PRINCE study provided a version of RIs suitable for most of regions in China. This first harmonized pediatric RIs of CBC across China provided a robust database to understand the dynamic changes of hematologic parameters from birth to adolescence, and will contribute to clinical diagnosis and prognosis evaluation for pediatric patients as well.

Reference intervals of 14 biochemical markers for children and adolescence in China: the PRINCE study.

OBJECTIVES: The Pediatric Reference Intervals in China (PRINCE) was initiated to establish the reference intervals (RIs) of Chinese children, as well as to make it possible to compare the variability of biochemical markers among countries internationally. METHODS: Healthy participants, aged up to 20 years, from 11 provinces across China, were enrolled in PRINCE and according to a standard screening procedure, that included a questionnaire survey, physical examinations and laboratory tests. Fasting venous blood specimens were collected. All serum specimens were analyzed with Cobas C702 in the center laboratory, i.e. clinical laboratory of Beijing Children's Hospital, with certified qualification (ISO15189). The nonparametric method recommended by Clinical Laboratory Standards Institute guidelines, was used to calculate the age- and sex-specified RIs. RESULTS: Among the 15,150 participants enrolled, 12,352 children (6,093 males and 6,259 females) were included to calculate RIs. The RIs for total protein, albumin, globulin, calcium, phosphate, potassium, sodium, chlorine, alkaline phosphatase, γ-glutamyl transpeptadase, alanine aminotransferase, aspartate aminotransferase, creatinine and urea were established by age- or sex-partitions. Most biochemical markers displayed larger variability and higher dispersion during the periods between 28 days and 1 year old, and included 4-6 age partitions commonly during 1 to <20 years old. In addition, differences of RIs between sexes usually occurs around the initiation of puberty at 12-13 years old. CONCLUSIONS: The age- and sex-specified RIs of 14 biochemical markers in PRINCE study can provide a solid reference, which will be transferred into relevant RIs for other clinical laboratory's platforms according to the CLSI guidelines.

Silver Nanoparticles Based Ink with Moderate Sintering in Flexible and Printed Electronics.

Printed electronics on flexible substrates has attracted tremendous research interest research thanks its low cost, large area production capability and environmentally friendly advantages. Optimal characteristics of silver nanoparticles (Ag NPs) based inks are crucial for ink rheology, printing, post-print treatment, and performance of the printed electronics devices. In this review, the methods and mechanisms for obtaining Ag NPs based inks that are highly conductive under moderate sintering conditions are summarized. These characteristics are particularly important when printed on temperature sensitive substrates that cannot withstand sintering of high temperature. Strategies to tailor the protective agents capping on the surface of Ag NPs, in order to optimize the sizes and shapes of Ag NPs as well as to modify the substrate surface, are presented. Different (emerging) sintering technologies are also discussed, including photonic sintering, electrical sintering, plasma sintering, microwave sintering, etc. Finally, applications of the Ag NPs based ink in transparent conductive film (TCF), thin film transistor (TFT), biosensor, radio frequency identification (RFID) antenna, stretchable electronics and their perspectives on flexible and printed electronics are presented.

Multilocus sequence typing and clonal population genetic structure of Cyclospora cayetanensis in humans.

To investigate the prevalence of Cyclospora cayetanensis in a longitudinal study and to conduct a population genetic analysis, fecal specimens from 6579 patients were collected during the cyclosporiasis - prevalent seasons in two urban areas of central China in 2011-2015. The overall incidence of C. cayetanensis infection was 1·2% (76/6579): 1·6% (50/3173) in Zhengzhou and 0·8% (26/3406) in Kaifeng (P 0·05). All the isolates clustered in the C. cayetanensis clade based on the small subunit ribosomal RNA gene sequence phylogenetic analysis. There were 45 specimens positive for all the five C. cayetanensis microsatellite loci, and formed 29 multilocus genotypes (MLGs). The phylogenetic relationships of 54 distinct MLGs (including 25 known reference MLGs), based on the concatenated multilocus sequences, formed three main clusters. A population structure analysis showed that the 79 isolates (including 34 known reference isolates) of C. cayetanensis produced three distinct subpopulations based on allelic profile data. In conclusion, we determined the frequency of C. cayetanensis infection in humans in Henan Province. The clonal population structure of the human C. cayetanensis isolates showed linkage disequilibrium and three distinct subpopulations.

[Application of eight-probe fluorescence in situ hybridization and R-banding karyotype analysis for the diagnosis of acute lymphoblastic leukemia].

OBJECTIVE: To assess the value of eight-probe fluorescence in situ hybridization (FISH) and R-banding karyotype analysis for the diagnosis of acute lymphoblastic leukemia (ALL). METHODS: With the eight-probe FISH (using probes for MYC, P16, E2A, CHIC2/D10Z1/D17Z1, TEL/AMLl, MLL, BCR/ABL1, and IGH) and R-banding karyotype analysis, 237 cases of ALL were analyzed. RESULTS: Cytogenetic changes were detected in 135 (56.96%) of all cases, which have involved MYC, P16, E2A, CHIC2/D10Z1/D17Z1, TEL/AMLl, MLL, BCR/ABL1, and IGH polyploidies. R-banding karyotype analysis has only detected abnormalities in 48 of such cases, in addition with 14 abnormalities missed by the FISH probes, which have given a total positive rate of 26.16%. The detection rate of the two methods has differed significantly(P<0.05). CONCLUSION: Compared with the R-banding karyotype analysis, the eight-probe FISH is more accurate and efficient. Diagnosis of cytogenetic abnormalities for children with ALL using the combined method can provide a basis for evaluation of prognosis as well as personalized therapy.

[Morphology and pathogenesis of 47, XYY/47, XY, +mar identified in patients with super male syndrome].

OBJECTIVE: To explore the source and morphology of supernumerary markers from patients with 47,XYY/47,XY, +mar and supermale syndrome. METHODS: Conventional GTG banded karyotyping and dual-color fluorescence in situ hybridization (FISH) were performed on 21 such patients. RESULTS: Among these cases, 18 had their small supernumerary marker derived from the Y chromosome. Three were derived from autosomal chromosomes. Those derived from Y chromosome were small fragments with centromeres, while those derived from autosomes were in the ring form. CONCLUSION: In children with supermale syndrome and 47,XYY/47,XY,+ mar, the supernumerary marker chromosomes primarily derive from sex chromosomes. These small chromosomes mainly have the forms of small segments with centromeres or rings. For such children, molecular cytogenetic analysis can facilitate genetic counseling and prenatal diagnosis.

[A novel splicing mutation in COL1A1 gene caused type I osteogenesis imperfecta in a Chinese family].

OBJECTIVE: To study a family affected with osteogenesis imperfecta for potential mutations in COL1A1 gene. METHODS: Clinical data of an affected family was collected. Potential mutation of the COL1A1 gene was screened using polymerase chain reaction and direct sequencing. Suspected mutation was detected in 20 unaffected relatives and 200 unrelated healthy controls. RESULTS: Analysis of RNA splicing has revealed a c.3208G/A mutation, which created a new splice sites and led to a frameshift mutation. The same mutation was not detected in the unaffected relatives or the 200 healthy controls. CONCLUSION: Mutations of the COL1A1 gene are one of the major causes of osteogenesis imperfecta in Chinese population. Our finding has enriched the mutation spectrum of type I collagen genes.

[Identification of a novel splicing mutation in COL1A1 gene in a Chinese family affected with typeâ osteogenesis imperfecta].

OBJECTIVE: To investigate the genetic cause for a large family affected with typeⅠosteogenesis imperfecta. METHODS: Genomic DNA was extracted from peripheral venous blood samples. The entire coding region and intron-exon boundaries of the COL1A1 gene were subjected to PCR amplification and direct sequencing. Total RNA was also extracted from immortalized B cell lines from the patients, with the first strand of cDNA synthesized with an oligo(dT)18 primer. The PCR products were directly sequenced using the TA cloned plasmid. RESULTS: A c.3208G>A mutation has been identified in the COL1A1 gene, which can alter the splicing pattern of mRNA. CONCLUSION: A novel splicing mutation c.3208G>A of the COL1A1 gene probably underlies the disease.

Straw and phosphorus applications promote maize (Zea mays L.) growth in saline soil through changing soil carbon and phosphorus fractions.

Introduction: Straw return has been widely recognized as an important carbon (C) enhancement measure in agroecosystems, but the C-phosphorus (P) interactions and their effects on plants in saline soils are still unclear. Methods: In this study, we investigated the effects of straw return and three P application levels, no P fertilizer (Non-P), a conventional application rate of P fertilizer (CP), and a high application rate of P fertilizer (HP), on maize growth and soil C and P fractions through a pot experiment. Results and discussion: The results revealed that the dry matter weight of maize plant was no difference between the two straw return levels and was 15.36% higher under HP treatments than under Non-P treatments. Plant nutrient accumulations were enhanced by straw addition and increased with increasing P application rate. Straw application reduced the activities of peroxidase (POD), superoxide dismutase (SOD), catalase, and the content of malondialdehyde (MDA) in maize plants by 31.69%, 38.99%, 45.96% and 27.04%, respectively. P application decreased SOD, POD activities and MDA content in the absence of straw. The contents of easily oxidized organic carbon (EOC), particulate organic carbon (POC) and the ratio of POC/SOC in straw-added soils were 10.23%, 17.00% and 7.27% higher, respectively, than those in straw-absent soils. Compared with Non-P treatments, HP treatments led to an increase of 12.05%, 23.04% in EOC, POC contents respectively, while a decrease of 18.12% in the contribution of MAOC to the SOC pool. Straw return improved the P status of the saline soil by increasing soil available P (14.80%), organic P (35.91%) and Ca2-P contents (4.68%). The structural equation model showed that straw and P applications could promote maize growth (indicated by dry matter weight, P accumulation, antioxidant enzyme activity and MDA content) through improving soil C and P availabilities. Conclusion: This study provides evidence that straw return together with adequate P supply in saline soil can promote crop nutrient accumulation, attenuate the oxidation damage on crop growth, and be beneficial for SOC turnover and soil P activation.

Printed and Flexible Capacitive Pressure Sensor with Carbon Nanotubes based Composite Dielectric Layer.

Flexible pressure sensors have attracted tremendous attention from researchers for their widely applications in tactile artificial intelligence, electric skin, disease diagnosis, and healthcare monitoring. Obtaining flexible pressure sensors with high sensitivity in a low cost and convenient way remains a huge challenge. In this paper, the composite dielectric layer based on the mixture of carbon nanotubes (CNTs) with different aspect ratios and polydimethylsiloxane (PDMS) was employed in flexible capacitive pressure sensor to increase its sensitivity. In addition, the screen printing instead of traditional etching based methods was used to prepare the electrodes array of the sensor. The results showed that the aspect ratio and weight fraction of the CNTs play an important role in improving the sensitivity of the printed capacitive pressure sensor. The prepared capacitive sensor with the CNTs/PDMS composite dielectric layer demonstrated a maximum sensitivity of 2.9 kPa-1 in the pressure range of 0-450 Pa, by using the CNTs with an aspect ratio of 1250-3750 and the weight fraction of 3.75%. The mechanism study revealed that the increase of the sensitivity of the pressure sensor should be attributed to the relative permittivity increase of the composite dielectric layer under pressure. Meanwhile, the printed 3 × 3 and 10 × 10 sensor arrays showed excellent spatial resolution and uniformity when they were applied to measure the pressure distribution. For further applications, the flexible pressure sensor was integrated on an adhesive bandage to detect the finger bending, as well as used to create Morse code by knocking the sensor to change their capacitance curves. The printed and flexible pressure sensor in this study might be a good candidate for the development of tactile artificial intelligence, intelligent medical diagnosis systems and wearable electronics.

Molecular characterization of three intestinal protozoans in hospitalized children with different disease backgrounds in Zhengzhou, central China.

BACKGROUND: Cryptosporidium spp. and Giardia duodenalis are major intestinal pathogens that can cause diarrheal diseases in humans, especially children. Enterocytozoon bieneusi is another parasite which can cause gastrointestinal tract disorders, with diarrhea being the main clinical symptom. However, few genetic studies of these parasites in pediatric inpatients in China have been published. METHODS: To assess the genetic characteristics and epidemiological status of these parasites, a total of 2284 fecal samples were collected from children in the pediatric departments of three hospitals in Zhengzhou, central China, and screened for these protozoans with PCR, based on the small subunit ribosomal RNA (SSU rRNA) genes of Cryptosporidium spp. and G. duodenalis and the internal transcribed spacer (ITS) of E. bieneusi. RESULTS: Six (0.26%), 14 (0.61%), and 27 (1.18%) of the samples were positive for Cryptosporidium spp., G. duodenalis and E. bieneusi, respectively. Of the 12 successfully sequenced G. duodenalis isolates, four were identified as assemblage A and eight as assemblage B. In subtype and multilocus genotype (MLG) analyses, C. parvum IIdA19G1 (n = 4) and two novel G. duodenalis MLGs belonging to subassemblage AII (n = 3) and BIV (n = 5) were successfully identified. The E. bieneusi isolates included genotypes D (n = 17), J (n = 2), PigEBITS7 (n = 1), BEB6 (n = 1), and CM8 (n = 1). This is the first report of C. parvum subtype IIdA19G1 in HIV-negative children and E. bieneusi genotype CM8 in humans. CONCLUSIONS: The dominance of zoonotic C. parvum subtype IIdA19G1 indicates that this parasite is turning into zoonotic origin from human-to-human transmission. The phylogenetic analysis also revealed the zoonotic origins and anthroponotic transmission potential of G. duodenalis and E. bieneusi, suggesting more efforts must be made to minimize the threat these pathogens pose to public health.

Nano-Silver Ink of High Conductivity and Low Sintering Temperature for Paper Electronics.

Highly conductive ink with low sintering temperature is important for printed electronics on paper substrate. Silver nanoparticles (Ag NPs) of different average radii ranging from 48 to 176 nm were synthesized by adjusting the Ag+ concentration in the reaction process. The electric resistivity of the Ag NP-based ink film in relation to Ag NP size, sintering temperature, amount of PVP capping agent on Ag NP surface, and morphology evolution of the film during heating process was investigated. It was found that the resistivity of the films reduced very rapidly with increasing particle size due above all to reduced amount of protective agent capping on the Ag NPs. A semi-empirical relationship between the resistivity and the particle size was proposed. With the help of this mathematical expression, one gains both systematic and detailed insight to the resistivity evaluation with regard to the Ag particle size. The optimal electric resistivity of 4.6 µΩ cm was achieved at 140 °C for 10 min which was very close to the resistivity value of bulk Ag (1.58 µΩ cm). Mechanical flexibility of the printed electronics with the Ag NP-based ink on paper substrates was investigated. The prints on the art coated paper exhibited better flexibility compared to that on the photopaper. This might be attributed to the surface coating composition, surface morphology of the paper, and their corresponding ink absorption property.

Pediatric reference intervals in China (PRINCE): design and rationale for a large, multicenter collaborative cross-sectional study.

There is a lack of accurate pediatric reference intervals (RIs) in China, with most commonly used RIs established without consideration of the effect of age and gender. The Pediatric Reference Intervals in China (PRINCE) project aims to establish and verify pediatric RIs for 31 common laboratory measurands. The project will be a large, multicenter cross-sectional study: 14,490 healthy children and adolescents aged up to 19 years will be surveyed by 10 children's hospitals and one pediatric department of a university hospital. To evaluate the feasibility and efficiency of the study methods, 602 children were surveyed in the pilot phase of the PRINCE study in April 2017: it found that some measurands were distinctly age dependent and that there were differences between values for males and females. The results of the pilot study affirmed the necessity of the PRINCE project for Chinese pediatrics. The pilot also indicated potential difficulties in the full survey, e.g., difficulties in recruiting children aged under 3 years and insufficient collection of blood samples from infants. The operation of the PRINCE project has been modified based on the findings in the pilot study toward improving the validity of the PRINCE project and promoting its openness and transparency.

A novel splicing mutation in COL1A1 gene caused type I osteogenesis imperfecta in a Chinese family.

Osteogenesis imperfect (OI) is a heritable connective tissue disorder with bone fragility as a cardinal manifestation, accompanied by short stature, dentinogenesis imperfecta, hyperlaxity of ligaments and skin, blue sclerae and hearing loss. Dominant form of OI is caused by mutations in the type I procollagen genes, COL1A1/A2. Here we identified a novel splicing mutation c.3207+1G>A (GenBank ID: JQ236861) in the COL1A1 gene that caused type I OI in a Chinese family. RNA splicing analysis proved that this mutation created a new splicing site at c.3200, and then led to frameshift. This result further enriched the mutation spectrum of type I procollagen genes.