Progress and prospect of global vaccine research and development / 中国药科大学学报

@#Abstract: The emerging infectious diseases have become an important risk factor affecting human public health. Vaccination remains the most critical approach to the prevention and control of such diseases. Since the outbreak of the COVID-19 epidemic, lots of transformational basic innovative vaccine technologies and strategies have been developed. The third-generation vaccine technology represented by mRNA vaccine has gradually become a new approach to the research and development of vaccines. This paper introduces the characteristics of different vaccine technologies in recent years, and summarizes the latest research progress in current vaccine products based on different platforms, so as to provide experience and reference for future research and development of vaccines.

The Research Progress of Essential Hypertension Related Gene DNA Methylation / 现代生物医学进展

Hypertension is a common and chronic disease,and is also the mainly risk factor of cardio-cerebrovascular disease.Essential hypertension is a complex disease caused by the common function of multiple genes and environmental factors,but the exact pathogenesis is still unclear.With the study continues,the role of DNA methylation and other epigenetic factors in pathological process with essential hypertension (EH) gradually be taken seriously.This review summarizes the research progress of some essential hypertension related methylation genes' function in the course of hypertension,to explain the relationship between DNA methylation markers which can be influenced by environment factor and essential hypertension and help us have a further understanding about the hypertension pathogenesis.

Analysis of clinical phenotype and genotype of unstable Hemoglobin Rush / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the hematological and genetic characteristics of unstable hemoglobin Rush (Hb Rush) and compound heterozygote of Hb Rush and thalassemia.</p><p><b>METHODS</b>Peripheral blood samples and genomic DNA from three patients (including two ethnic Dai and one Han Chinese) with anemia of undetermined origin were collected. Hematological phenotypes of these patients were determined through red blood cell analysis and hemoglobin electrophoresis. Genotypes of alpha- and beta-globin genes, -158 XmnⅠ polymorphic site ofγ promoter region, and haplotypes of 7 polymorphic restriction sites in the beta-globin gene cluster were determined using PCR-based methods and DNA sequencing.</p><p><b>RESULTS</b>All patients have presented hypochromic microcytic anemia and hemoglobin fraction with significant increased measurement (30.5%-59.2%) in the region of fetal hemoglobin during alkaline medium electrophoresis. DNA analysis suggested that all patients have carried mutations leading to the unstable hemoglobin Rush (HBB codon 101, GAG>CAG, Glu>Gln). Two of them were compound heterozygotes of Hb Rush and thalassemia mutations of -α,CD17 and Hb E, respectively. Hb Rush mutation was associated with various haplotypes of the β-globin gene cluster. No significant association was found between increased abnormal hemoglobin fraction in the region of Hb F and the polymorphism ofγ promoter or large deletion of the beta-globin gene cluster.</p><p><b>CONCLUSION</b>This study has confirmed the distribution of Hb Rush among various Chinese populations and is the third report of its kind. Hb Rush can result in increased measurement of hemoglobin fraction in the region of fetal hemoglobin (Hb F) during routine hemoglobin electrophoresis under alkaline condition. Hb Rush heterozygote alone can lead to hypochromic microcytic anemia and thalassemia-like phenotype. Prenatal diagnosis of Hb Rush is necessary for carriers.</p>

Mechanisms of aspirin-induced apoptosis in EBV-transformed human B lymphocytes / 中国药理学通报

Aim To investigate the effects of aspirin on Epstein-Barr virus (EBV)-transformed human B-lym-phocytes.Methods EBV-transformed human B-lym-phocytes were treated with certain concentrations of as-pirin.Cellular proliferation was analyzed by MTT as-say.Further evaluation of apoptosis of aspirin-treated cells was performed through light-field microscope, transmission electronic microscope(TEM),propidium iodide(PI)staining and flow cytometric analysis and DNA electrophoresis. Finally, immunoblot analysis was used to determine the expression levels of apopto-sis-associated proteins, proteins involved in mTOR pathway and PU.1 -Bim axis.Results Aspirin treat-ment inhibited proliferation of EBV-transformed human B-lymphocytes.We observed that aspirin treatment in-duced apoptosis in EBV-transformed human B-lympho-cytes,resulting in the decreased number and size of cells.Ultramicroscopic structural analysis via TEM in-dicated that aspirin treatment deformed the cellular nu-cleus,and led to peripheral chromatin and cytoplasmic vacuole.PI staining and flow cytometric analysis indi-cated that aspirin increased the permeability of cell membrane and decreased the viability of treated cells. Agarose electrophoresis revealed DNA smear in aspirin-treated cells.Mechanistically,mTOR signaling was in-hibited in aspirin-treated cells,as evidenced by the de-creased phosphorylation of S6K1 and S6 via immunob-lot analysis.Aspirin treatment led to the decrease of hematopoietic transcription factor PU.1 .Consequently, pro-apoptotic Bim, apoptosis-associated proteins caspase-3 and PARP were activated in aspirin-treated cells.Conclusion Aspirin may show anti-lymphoma effects via its inhibition of proliferation and induction of apoptosis of EBV-transformed human B-lymphocytes, in which mTOR signal pathway and PU.1 -Bim axis may be involved.

Impact of natural selection on the polymorphism of HLA-G 3'UTR among five ethnic Chinese populations / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the impact of natural selection and genetic background on the polymorphisms of HLA-G 3-untranslated regions (UTR) among five ethnic Chinese populations.</p><p><b>METHODS</b>PCR and DNA sequencing were used to determine the polymorphisms among 432 individuals from the five ethnic populations. Their genetic background was determined by genotyping of 10 short tandem repeats (STRs).</p><p><b>RESULTS</b>Eight variations were identified among Gelao, Mongolian and Kirgiz populations, while only 7 were found in Shui and Dai people. For all 3 southern populations (Gelao, Shui, and Dai), the observed heterozygosites (Ho) was higher than expected heterozygosities (He). But this was reversed for the 2 northern populations (Mongolian and Kirgiz). The Ho and He of the 10 neutral STRs were in random distribution. Ewens-Watterson testing based on haplotypes of the HLA-G 3'UTR has suggested that a natural selection had occurred in the region where Dai and Shui had inhabited, but not in the northern region where Mongolian and Kirgiz population inhabited. Polygenetic trees based on the HLA and STRs were also different.</p><p><b>CONCLUSION</b>The HLA-G 3'UTR of Dai and Shui people who lived in southern China may have subjected to a selection pressure. Based on current knowledge, this pressure may have been driven by a pathogenic selection.</p>

Association of three polymorphisms in the 3' untranslated region of the HLA-G gene with systemic lupus erythematosus in a population from Yunnan / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of three polymorphisms (14-bpINS/DEL, +3035C/T and +3142C/G) in the 3' untranslated region (3'UTR) of HLA-G gene and systemic lupus erythematosus (SLE) in Yunnan.</p><p><b>METHODS</b>A case-control study has been carried out on 206 SLE patients and 212 healthy controls. Genotypes of 14-bpINS/DEL (rs1704), +3035C/T (rs17179108) and +3142C/G (rs1063320) loci of 3'UTR of the HLA-G gene were determined with DNA sequencing.</p><p><b>RESULTS</b>Allelic and genotypic frequencies of 14-bpINS/DEL and +3142C/G did not differ significantly between the two groups (P > 0.05). The frequencies of +3035T allele was significantly higher in the SLE group compared with the control group (P < 0.01, OR=1.604, 95% CI: 1.186-2.169). With a dominant inheritance model, the odd ratio of dominant genotype (CT+TT) was 2.004 (95% CI: 1.345-2.987, P=0.0006) in the SLE group.</p><p><b>CONCLUSION</b>The 14-bpINS/DEL and +3142C/G polymorphisms in the 3'UTR of the HLA-G gene are not associated with susceptibility to SLE in Yunnan, whilst the T allele of +3035C/T may be a risk factor for SLE.</p>

A study of the relationship between MICA gene and systemic lupus erythematosus / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between major histocompatibility complex class I chain-related A(MICA) gene and systemic lupus erythematosus (SLE).</p><p><b>METHODS</b>The alleles and frequencies of exons 4 and 5 of MICA gene were determined in 70 cases of SLE and 152 controls of Yunnan Hans by STR genotyping, polymerase chain reaction, single strand conformation polymorphism and bidirection DNA sequencing.</p><p><b>RESULTS</b>Five alleles of exon 5 and 10 alleles of exon 4 were found in this study. The frequency of each allele was determined in patients and controls. There was no significant difference between the two groups in exons 4 and 5 of MICA gene.</p><p><b>CONCLUSION</b>Exons 4 and 5 of MICA were not related to SLE in Yunnan Hans.</p>