Paternal genetic structure analysis of the modern Han populations based on Y-SNP and Y-STR.

The Han populations represent the largest ethnic group in China. Previous studies have primarily focused on investigating their genetic origins, migration and integration, as well as paternal genetic relationships within specific regional Han populations. However, a comprehensive analysis of the global paternal genetic structure of Han populations is lacking. In this study, we performed Y-chromosome sequencing on 362 unrelated male samples from Chinese Han individuals collected from Qinghai, Sichuan and Liaoning provinces. We then integrated relevant data from reported studies. Our final dataset comprised 1830 samples from 16 Han populations across 15 provinces in China, encompassing information on 89 Y-SNPs and 16 Y-STRs. Statistical analyses were conducted to assess Y-STR haplotype diversity (HD) and Y-SNP haplogroup frequencies. Additionally, we employed principal component analysis (PCA), phylogenetic tree and haplotype network to explore genetic differentiation within Han populations and the genetic relationships between Han populations and ethnic minorities surrounding them. Our results demonstrated that the O-M175 haplogroup represents the predominant paternal lineage in Han populations, with frequencies ranging from 60.53% (Qinghai Han) to 92.7% (Guangdong Han). Moreover, the subclades downstream of O-M175 showed distinct regional variations in their distribution patterns. The O2-M122 haplogroup was prevalent in all Han populations and demonstrated a gradual decline in frequency from north to south. Conversely, the distribution frequency of the O1b-M268 haplogroup decreased from south to north, particularly showed significant presence among Han populations in the Lingnan region. Haplogroup O1a-M119 distributed more frequently in the central Han populations. Our findings revealed that Chinese Han populations can be categorized into three subgroups: northern, central, and southern. Notably, there were significant differences among Han in Qinghai and other regions. Regarding the genetic relationships between Han populations and surrounding ethnic minorities, we observed a closer genetic affinity between different Han populations, but northern Han demonstrated a stronger relationship with the Hui ethnic group, while southern Han exhibited a closer connection with the Gelao and Li ethnic groups. In summary, this study presented a systematic analysis of haplogroup distribution, genetic substructure of Han populations and genetic relationships between Han populations and surrounding ethnic minorities based on 89 Y-SNPs and 16 Y-STRs systematically. Our research supplemented valuable insights into population genetics and forensic genetics, and provided data support for the forensic application of Y chromosome. The integration of Y-SNP haplogroups with Y-STR haplotypes offers enhanced understanding of the genetic substructure within Han populations, which holds significance for both population genetics research and forensic science applications.

[Levels and Clinical Significances of sPD-1 and sPD-L1 in Peripheral Blood of Lymphoma Patients].

OBJECTIVE: To observe the levels of soluble programmed cell death protein 1 (sPD-1) and soluble programmed cell death ligand 1 (sPD-L1) in peripheral blood of lymphoma patients, and reveal their clinical significances. METHODS: The peripheral blood specimens and clinical data of 64 newly diagnosed lymphoma patients and 30 healthy volunteers were collected. The levels of sPD-1 and sPD-L1 were detected by enzyme-linked immunosorbent assay (ELISA), and their correlations with clinical characteristics of the patients including pathological type, stage, lactate dehydrogenase (LDH) level, T cell subsets were analyzed. RESULTS: The levels of both sPD-1 and sPD-L1 in peripheral blood of lymphoma patients were higher than those of normal controls (P <0.05). There were no significant differences in sPD-1 and sPD-L1 levels in peripheral blood between Hodgkin lymphoma and non-Hodgkin lymphoma patients. Different pathological subtypes of lymphoma had different levels of sPD-1. The level of sPD-1 in patients with T-cell lymphoma was higher than that in patients with B-cell lymphoma (P =0.001). The levels of both sPD-1 and sPD-L1 in patients with Ann Arbor stage III and IV were higher than those in patients with stage I and II (P <0.05). The level of sPD-L1 in patients with abnormally increased LDH was higher than that in patients with normal LDH (P =0.001), but there was no significant difference in sPD-1 level. T cell subset analysis showed that the level of sPD-L1 was negatively correlated to CD4+ T cell content (r =-0.265). CONCLUSION: The levels of sPD-1 and sPD-L1 in peripheral blood of lymphoma patients are related to the pathological type, Ann Arbor stage, LDH content and T cell subsets, and will be potential biomarkers in predicting the prognosis of lymphoma.

Effects of hypoxia on DNA hydroxymethylase Tet methylcytosine dioxygenase 2 in a KG-1 human acute myeloid leukemia cell line and its mechanism.

Hypoxia is involved in the epigenetic modification of leukemia. As an important DNA hydroxymethylase and a tumor suppressor gene, the expression regulating mechanism of Tet methylcytosine dioxygenase 2 (TET2) remains unclear. The aim of the present study was to explore whether hypoxia and hypoxia-inducible factor 1α (HIF-1α) regulate TET2 gene expression and its demethylation function in acute myeloid leukemia (AML). The human AML cell line KG-1 was used in the present study. The results demonstrated that hypoxia could increase proliferation, enhance metabolism and inhibit apoptosis in KG-1 cells, as detected by the cell counting kit-8 assay, lactate dehydrogenase assay and Annexin V-FITC/propidium iodide staining, respectively. Hypoxia reduced the genome methylation status in KG-1 cells detected using 5-methylcytosine and 5-hydroxymethylcytosine detection kits. In addition, HIF-1α overexpression increased TET2 expression, 5-hmC level and cyclin-dependent kinase inhibitor 2B [p15(INK4B)] gene demethylation compared with the HIF-1α non-overexpression group in KG-1 cells detected by reverse transcription-quantitative PCR, western blotting, 5-hydroxymethylcytosine detection kits and methylation-specific PCR, respectively. The inhibition of HIF-1α by inhibitor YC-1 reduced demethylation in KG-1 cells by decreasing TET2 expression. It was also revealed that HIF-1α could enhance TET2 transcriptional activity by binding to the hypoxia response element of the TET2 gene promoter region using chromatin immunoprecipitation and luciferase reporter gene assays. TET2 may be a potential target gene regulated by HIF-1α. Hypoxia was demonstrated to regulate the expression of TET2 by HIF-1α, which in turn affected the methylation and expression of downstream target genes and served a role in the occurrence and progression of leukemia. In the present study, the association between hypoxia metabolism and epigenetic regulation in AML was investigated and the findings provided a new idea and experimental basis for the diagnosis and treatment of hematologic malignancies.