In the context of delayed marriage and parenthood, decreased willingness in having children, and population aging in China, maternal and child health has become an important and urgent issue. Being essential platforms for research in maternal and child health, the importance of birth cohorts has been widely recognized. In the past 20 years, tens of birth cohorts have been established in major cities and regions of China, with cohorts ranging from thousands to hundreds of thousands. These cohorts, particularly those large ones launched in recent years, have collected a wide spectrum of data and biological samples from mothers and children. Although they have made considerable preliminary achievements, there remain difficulties and challenges. The significant challenges include small and medium-sized cohorts' lacking of clear research themes; insufficient recognition of and emphasis on behavioral and social determinants of health while emphasizing biological determinants of health; variations in types of variables and quality of data collected, which make it difficult for cohorts to be merged and shared; lack of and difficulties in long-term follow-up; significant uncertainties in resources for long-term sustention of the cohorts, and so on. So, we argue that birth cohorts should focus on essential and urgent issues in maternal and child health in the country and seek recognition and support from the government and the entire society. Last but not least, the overall success of birth cohorts in the country requires scientists to be not only academically capable, but also realistic, persistent, altruistic, and collaborative.
Background: Biliary atresia (BA) is considered to be an autoimmune-mediating inflammatory injury. The pathogenesis of BA has been proposed with the clonal transformation of T cells expressing analogous T-cell receptor β-chain variable regions (TRBVs). Methods: The TRBV profile of the peripheral blood mononuclear cells (PBMCs) in infants with BA and control infants (healthy donors, HDs), respectively, were characterized by using high-throughput sequencing (HTS). The diversity of T cells was analyzed based on the frequency of complementarity-determining region 3 (CDR3) or V(CDR3)J. Moreover, the correlation between absolute lymphocyte count (ALC) and lactate dehydrogenase (LDH) or diversity (clonality) indices, respectively, were analyzed for subjects with BA and HD. Results: The diversity indices of CDR3, V(CDR3)J in BA are lower than those in subjects with HD, in addition, there are significantly different levels of neutrophile, neutrophile/lymphocyte ratio (NLR), and LDH between groups of BA and HD. The correlation between ALC and diversity index is significant in subjects with HD but is not for subjects with BA. Conversely, the relationship between ALC and LDH is significant in subjects with BA but is not for subjects with HD. Moreover, 12 CDR3 motifs are deficient or lower expression in BA compared with that in the HD group. Conclusion: Our results demonstrate that the profile of TRBV repertoire is significantly different between subjects with BA and HD, and suggest that the immune imbalance and elevated LDH level are associated with the pathogenesis of BA. Moreover, the values of neutrophile, NLR, and LDH could be used for the differential diagnosis of BA.
Abstract Renal cell carcinoma (RCC) is infrequent in the pediatric population. In addition, till date, only a few reports have summarized the characteristics of pediatric RCC and differences between pediatric and adult RCC. Therefore, the current study aimed to investigate the clinical characteristics of RCC in children and adolescents, and identify the differences between children and adolescent patients and adult patients through literature retrieval. The data of 13 pediatric patients diagnosed with RCC at the Children's Hospital of Zhejiang University School of Medicine between 2005 and 2019 were retrospectively analyzed. Three patients were aged <5 years, 2 were aged 6 to 10 years, and 8 were aged 11 to 18 years. Among the 13 patients, common clinical manifestations included abdominal pain in 5 patients, gross hematuria in 4, and an abdominal mass in 1, while the other 3 patients were incidentally detected after an abdominal contusion. The pathological types were microphthalmia family translocation RCC in 9 patients, clear-cell RCC in 2, papillary RCC in 1, and unclassified in 1. All the children underwent radical nephrectomy, including 2 patients with advanced disease who underwent preoperative transcatheter arterial chemoembolization. The mean follow-up time was 58.6 months. Two patients died after 4 and 17 months of follow-up, respectively. In conclusion, microphthalmia family translocation renal cell carcinoma is the predominant type of pediatric RCC associated with advanced tumor stage. The early diagnosis and treatment of pediatric patients is important for improving prognosis. Nevertheless, future studies are urgently needed to determine the treatment for pediatric advanced RCC to increase the survival rate.
Human neutrophil peptides 1-3 (HNP1-3), also known as human α-defensins, are the most abundant neutrophil granule proteins. The genes that encode HNP1-3, DEFA1/DEFA3, exhibit extensive copy number variations, which correlate well with their protein levels. Human and mouse studies have shown that increased copy numbers of DEFA1/DEFA3 worsen sepsis outcomes. Additionally, high concentrations of HNP1-3 in body fluids have been reported in patients with sepsis. However, direct evidence for the pathogenic role of HNP1-3 proteins during sepsis progression is lacking. In current study, sepsis was induced by means of cecal puncture and ligation. Various doses of HNP-1 (low dose with 0.5 mg/kg body weight and high dose with 10 mg/kg body weight) or phosphate buffer saline were intraperitoneally administered to mice at six hours after sepsis onset. Survival rate was monitored, and vascular permeability, endothelial cell pyroptosis, and immunofluorescence of endothelial adherens junction protein vascular endothelial-cadherin were evaluated. The administration of a high dose of HNP-1 after sepsis onset led to increased mortality, more severe liver injury, and increased vascular permeability in the liver and mesentery. The injection of high dose of HNP-1 did not directly induce liver endothelial cell death but destroyed interendothelial junctions in the liver. Moreover, genetic deficiency of nucleotide-binding oligomerization domain-like receptor protein-3 or caspase-1 abrogated the high mortality and disrupted liver interendothelial junctions caused by high dose of HNP-1 during sepsis. This study directly demonstrates that neutrophil defensins play a key role in regulating endothelial stability during sepsis development.
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