[Determination of 13 kinds of free and bound phenolic acids in fruits by high-performance liquid chromatography-mass spectrometry].

OBJECTIVE: To establish a high-performance liquid chromatography-mass spectrometry(HPLC-MS/MS) method for detecting 13 kind of free and bound phenolic acids(chlorogenic acid, protocatechuic acid, ferulic acid, p-coumaric acid, gallic acid, gentisic acid, vanillic acid, caffeic acid, syringic acid, sinapic acid, rosmarinic acid, salicylic acid, p-hydroxybenzoic acid) in fruits, and optimize the pre-treatment conditions to meet the detection requirements for phenolic acid content in various types of fruits. METHODS: Free phenolic acids in fruits were extracted using methanol through ultrasonic extraction. Conjugated phenolic acids in the centrifuged residue were released by alkaline hydrolysis and extracted with ethyl acetate. The two extracts were combined, concentrated, and analyzed using HPLC-MS/MS. Separation was achieved using an Agilent ZORBAX SB-C_(18) chromatography column(3.0 mm×100 mm, 3.5 µm), and detection was performed in multiple reaction monitoring(MRM) mode. RESULTS: All 13 standard phenolic acids achieved complete separation within 10 minutes, with linear correlation coefficients greater than 0.998 and detection limits ranging from 0.172 to 3.471 ng/mL. After optimization of the pre-treatment method, the recovery rates of the method for four types of fruits-apples, strawberries, oranges, and peaches-ranged from 80.0% to 119.4%, and the precision were lower than 7.00%(n=6). The result of testing on four categories of twelve types of fruits demonstrated significant variations in the content of phenolic acids among different fruits, and within the same category, the composition of phenolic acids did not exhibit consistency. CONCLUSION: The HPLC-MS/MS method exhibits high sensitivity, precision, and accuracy. It is suitable for the detection of both free and bound phenolic acids in various types of fruits.

Biobanks in chronic disease management: A comprehensive review of strategies, challenges, and future directions.

Biobanks, through the collection and storage of patient blood, tissue, genomic, and other biological samples, provide unique and rich resources for the research and management of chronic diseases such as cardiovascular diseases, diabetes, and cancer. These samples contain valuable cellular and molecular level information that can be utilized to decipher the pathogenesis of diseases, guide the development of novel diagnostic technologies, treatment methods, and personalized medical strategies. This article first outlines the historical evolution of biobanks, their classification, and the impact of technological advancements. Subsequently, it elaborates on the significant role of biobanks in revealing molecular biomarkers of chronic diseases, promoting the translation of basic research to clinical applications, and achieving individualized treatment and management. Additionally, challenges such as standardization of sample processing, information privacy, and security are discussed. Finally, from the perspectives of policy support, regulatory improvement, and public participation, this article provides a forecast on the future development directions of biobanks and strategies to address challenges, aiming to safeguard and enhance their unique advantages in supporting chronic disease prevention and treatment.

Association of HLA-E single nucleotide polymorphisms with human myeloid leukemia.

Single nucleotide polymorphisms (SNPs) of HLA-E are related to the occurrence of many diseases, but their functions remain unclear. In this study, the function of SNPs at HLA-E rs76971248 and rs1264457 on the myeloid leukemia cells was analyzed by a progressive procedure, included genotyping, mRNA transcription, regulatory element, protein expression, and anti-tumor effect. The frequencies of rs76971248 G and rs1264457 G were found higher in myeloid leukemia patients than those in healthy blood donors (p < 0.05). For myeloid leukemia, rs76971248 T was protective, while rs1264457 G was susceptible. We also found that rs76971248 affected HLA-E mRNA transcription and membrane HLA-E (mHLA-E) expression in K562 cells through differently binding to transcription factor HOXA5 (p < 0.0001), while rs1264457 affected mHLA-E expression by changing mRNA transcription and an encoding amino acid (p < 0.01). In contrast, the expression of soluble HLA-E (sHLA-E) was not influenced by both rs1264457 and rs76971248. The higher HLA-E expression was detected among myeloid leukemia patients, and the K562 cells with higher HLA-E molecules played a significant inhibitory effect on the killing activity of NK-92MI cells (p < 0.05). In conclusion, the higher HLA-E expression of myeloid leukemia cells is promoted by rs76971248 G and rs1264457 G, which helps escape from NK-92MI cells' killing.

Single-cell transcriptomic profiling reveals immune cell heterogeneity in acute myeloid leukaemia peripheral blood mononuclear cells after chemotherapy.

PURPOSE: Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the rapid clonal expansion of abnormally differentiated myeloid progenitor cells residing in a complex microenvironment. However, the immune cell types, status, and genome profile of the peripheral blood mononuclear cell (PBMC) microenvironment in AML patients after chemotherapy are poorly understood. In order to explore the immune microenvironment of AML patients after chemotherapy, we conducted this study for providing insights into precision medicine and immunotherapy of AML. METHODS: In this study, we used single-cell RNA sequencing (scRNA-seq) to analyse the PBMC microenvironment from five AML patients treated with different chemotherapy regimens and six healthy donors. We compared the cell compositions in AML patients and healthy donors, and performed gene set enrichment analysis (GSEA), CellPhoneDB, and copy number variation (CNV) analysis. RESULTS: Using scRNA-seq technology, 91,772 high quality cells of 44,950 PBMCs from AML patients and 46,822 PBMCs from healthy donors were classified as 14 major cell clusters. Our study revealed the sub-cluster diversity of T cells, natural killer (NK) cells, monocytes, dendritic cells (DCs), and haematopoietic stem cell progenitors (HSC-Prog) in AML patients under chemotherapy. NK cells and monocyte-DCs showed significant changes in transcription factor expression and chromosome copy number variation (CNV). We also observed significant heterogeneity in CNV and intercellular interaction networks in HSC-Prog cells. CONCLUSION: Our results elucidated the PBMC single-cell landscape and provided insights into precision medicine and immunotherapy for treating AML.

Association between organic cation transporter genetic polymorphisms and metformin response and intolerance in T2DM individuals: a systematic review and meta-analysis.

Background: Variants in organic cation transporter (OCT) genes play a crucial role in metformin pharmacokinetics and are critical for diabetes treatment. However, studies investigating the effect of OCT genetic polymorphisms on metformin response have reported inconsistent results. This review and meta-analysis aimed to evaluate the associations between OCT genetic polymorphisms and metformin response and intolerance in individuals with type 2 diabetes mellitus (T2DM). Method: A systematic search was conducted on PubMed, EMBASE, CNKI, WANFANG DATA, and VIP database for identifying potential studies up to 10 November 2022. The Q-Genie tool was used to evaluate the quality of included studies. Pooled odds ratios (OR) or standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated to determine the associations between OCT genetic polymorphisms and metformin response and intolerance that were reflected by glycemic response indexes, such as glycated hemoglobin level (HbA1c%) or change in glycated hemoglobin level (ΔHbA1c%), fasting plasma level (FPG) or change in fasting plasma glucose level (ΔFPG), the effectiveness rate of metformin treatment, and the rate of metformin intolerance. A qualitative review was performed for the variants identified just in one study and those that could not undergo pooling analysis. Results: A total of 30 related eligible studies about OCT genes (SLC22A1, SLC22A2, and SLC22A3) and metformin pharmacogenetics were identified, and 14, 3, and 6 single nucleotide polymorphisms (SNPs) in SLC22A1, SLC22A2, and SLC22A3, respectively, were investigated. Meta-analysis showed that the SLC22A1 rs622342 polymorphism was associated with a reduction in HbA1c level (AA vs. AC: SMD [95% CI] = -0.45 [-0.73--0.18]; p = 0.001). The GG genotype of the SLC22A1 rs628031 polymorphism was associated with a reduction in FPG level (GG vs. AA: SMD [95 %CI] = -0.60 [-1.04-0.16], p = 0.007; GG vs. AG: -0.45 [-0.67-0.20], p < 0.001). No statistical association was found between the remaining variants and metformin response and intolerance. Conclusion: SLC22A1 rs622342 and rs628031 polymorphisms were potentially associated with glycemic response to metformin. This evidence may provide novel insight into gene-oriented personalized medicine for diabetes.

Genetic regulation of THBS1 methylation in diabetic retinopathy.

Background: Diabetic retinopathy (DR) is a common and serious microvascular complication of diabetes mellitus (DM), but its pathological mechanism, especially the formation mechanism of new blood vessels remains unclear. Thrombospondin-1 (THBS1) is a potent endogenous inhibitor of angiogenesis and it was found over expressed in DR in our previous study. Our study aimed to determine whether overexpression of THBS1 is associated with its promoter methylation level, and whether methylation of THBS1 is regulated by genetic variants in DR. Methods: Patients diagnosed with DR and DM patients without retinal problems were included in the case-control study. DNA methylation detection of THBS1 by bisulfite sequencing and genotyping of specific SNPs by MassARRAY analysis were performed in the patients recruited from 2019-2020. Real time quantitative PCR was performed to obtain mRNA expression of THBS1 in the patients recruited from August to October 2022. The differentially methylated CpG loci of THBS1 were identified by logistic regression, and associations between 13 SNPs and methylation levels of CpG loci were tested by methylation quantitative trait loci (meQTLs) analysis. Mediation analysis was applied to determine whether CpG loci were intermediate factors between meQTLs and DR. Results: 150 patients diagnosed with DR and 150 DM patients without retinal complications were enrolled in the first recruitment, seven DR patients and seven DM patients were enrolled in the second recruitment. The patients with DR showed promoter hypomethylation of THBS1 (P value = 0.002), and six out of thirty-nine CpG sites within two CpG islands (CGIs) showed hypomethylation(P value < 0.05). THBS1 mRNA expression in peripheral blood was significantly higher in DR patients than in DM patients. Five out of thirteen cis-meQTLs were identified to be associated with CpG sites: rs13329154, rs34973764 and rs5812091 were associated with cis-meQTLs of CpG-4 (P value=0.0145, 0.0095, 0.0158), rs11070177 and rs1847663 were associated with cis-meQTLs of CpG-2 and CpG-3 respectively (P value=0.0201, 0.0275). CpG-4 methylation significantly mediated the effect of the polymorphism rs34973764 on DR (B=0.0535, Boot 95%CI: 0.004~0.1336). Conclusion: THBS1 overexpression is related to THBS1 hypomethylation in patients with DR. DNA methylation may be genetically controlled in DR.

Exploration of the lower threshold of iodine intake in Southern Chinese young adults based on 'overflow theory' in an iodine balance study.

BACKGROUND: Appropriate iodine intake for adults is essential to reduce the prevalence of thyroid diseases, but there is little research data on iodine requirement of Chinese population. This study aimed to explore the iodine requirement of young adults to maintain a healthy status based on 'overflow theory'. METHODS: Iodine-balance experiment has been performed in this project. We conducted an 18-day study consisted of a 6-day acclimation period and 3 consecutive experimental stages in 37 Chinese healthy young adults (23 female and 14 male). Each stage was consumed for 4 days. Strictly-controlled low-iodine intake diets were provided for adults in the first period, an egg or 125mL milk was added in the second and third period, respectively. The dietary samples, 24-h urine specimens and faeces of volunteers were collected daily for assessment of iodine intake and excretion in volunteers. RESULTS: Mean values of iodine intake (22.7±3.6, 35.1±3.7, and 52.2±3.8µg/d), excretion (64.7±13.9, 62.3±12.6, and 94.3±14.5µg/d) and iodine balance (-35.2±19.5, -21.0±19.8, and -33.5±26.9µg/d) were significantly different among three periods for male (P<0.001 for all); mean values of iodine intake (16.6±3.1, 29.7±2.7, and 48.0±2.7µg/d), and excretion (47.0±9.9, 55.5±8.1, and 75.7±12.4µg/d) were significantly different among three periods for female (P < 0.001 for all). No significant difference was observed among the 3 periods for female in the iodine balance (-30.5±9.3, -25.9±7.3, and -27.6±12.1µg/d). The linear regression equation of iodine excretion on iodine intake was Y=0.979X+37.04 (male) and Y=0.895X+31.48 (female). Compared with stage 2, iodine excretion increments in stage 3 had exceeded the iodine intake increment for men. The ratio of increment was 1.675 for male when the average iodine intake was 52.2µg/d in stage 3. When the iodine excretion increment equaled to the iodine intake increment, the daily iodine intake of men was 47.0µg. CONCLUSION: We have evaluated the iodine requirement of young adults in southern China based on overflow theory. Our results indicate the lower limit of iodine requirement for Chinese young men is 47.0µg/d. The trial was registered at www.chictr.org.cn as ChiCTR1800014877.

Association of variations in the Fanconi anemia complementation group and prognosis in Non-small cell lung cancer patients with Platinum-based chemotherapy.

PURPOSE: To explore the associations between FANC (FANCA, FANCC, FANCE, FANCF, and FANCJ) single nucleotide polymorphisms (SNPs) and prognosis of non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. METHODS: According to the inclusion criteria, we selected 395 DNA samples from NSCLC patients for genotyping and combined with clinical data for Cox regression analysis and stratification analyses to assess relationships between overall survival (OS) and progression free survival (PFS) with SNPs genotypes. RESULTS: The results revealed that patients with FANCE rs6907678 TT genotype have a longer OS than TC and CC genotype (Additive model: P = 0.004, HR = 1.696, 95% CI = 1.186-2.425). In stratification analyses, Longer PFS is found in female, age ≤ 55 years old and non-smoking patients with FANCE rs6907678 TT genotype, and patients with TT genotypes were significantly had longer OS in male, age ＞55 years old, non-smoking, squamous cell carcinoma and stage IV stratification. CONCLUSION: Our data demonstrates that patients with FANCE rs6907678 TT genotype are contributed to better prognosis. FANCE rs6907678 may be used as a clinical biomarker for predicting the prognosis of NSCLC patients with platinum-based chemotherapy.

Characterization of alternatively spliced transcript variants of glycophorin A and glycophorin B genes in Chinese blood donors.

BACKGROUND AND OBJECTIVES: The molecular basis of MNS blood group variants is not fully clear yet. In this study, we have characterized mRNA variants of GYPA and GYPB genes to reveal whether alternative RNA splicing may cause antigenic diversity of the MNS system. MATERIALS AND METHODS: Total RNA was extracted from peripheral blood of Chinese blood donors and full-length cDNA products were generated. A nested polymerase chain reaction (PCR)-based method was established for fragment amplification and Sanger sequencing. Resulted full-length mRNA sequences were aligned with GYPA or GYPB genomic sequences respectively for exon identification. Amino acid (AA) sequences of GPA and GPB proteins were extrapolated and GYPA-EGFP, GYPB-EGFP fusion genes were generated to monitor subcellular distribution of the encoded glycophorin (GP) proteins. RESULTS: Totally 10 blood samples were analysed. GYPB mRNAs of all the subjects demonstrated frequent exon insertion or deletion whereas this kind of variation was only observed in 3 of 10 GYPA mRNA samples. None of the reported Miltenberger hybrids was detected in any of the mRNA samples. The alternative splicing resulted in changes of AA sequences in N-terminal domains where the MNS antigenic motifs resided; however, subcellular localizations of GP-EGFP fusion proteins showed that the above-mentioned AA changes did not affect cell surface distribution of the encoded GP proteins. CONCLUSIONS: Alternative RNA splicing may influence the antigenic features of GP proteins but not their cell surface distribution. Therefore, GYPA and GYPB mRNA characterization might be an invaluable supplement to serological phenotyping and DNA-based genotyping in MNS blood grouping.

Correlation of Human Leukocyte Antigen-E Genomic Polymorphism with Leukemia and Functional Study of Human Leukocyte Antigen-E Different Type Promoters.

Human leukocyte antigen (HLA)-E is one of the least polymorphic nonclassical major histocompatibility complex (MHC) I genes; its nucleotide variability can affect immune response. In this study, we assess the correlation between HLA-E polymorphism and leukemia and further study the transcriptional activity of promoter variation at nucleotide position-26. A total of 142 healthy blood donors and 111 leukemia patients were collected. The genomic sequence of HLA-E was amplified by high-fidelity reaction system and identified by Sanger and cloning sequencing. The dual luciferase reporter gene assay was used to detect the transcription activity of promoter variation at nucleotide position-26. In the HLA-E genomic sequence results, a total of 16 alleles and 32 genotypes were detected; the HLA-E*01:01:01:06 allele had a significantly lower frequency in leukemia patients than in healthy participants (p = 0.026 < 0.05). And the HLA-E*01:03:02:01, *01:03:02:01 genotype showed the greatest difference in frequency between the two groups of participants (p = 0.028 < 0.05). Eight HLA-E alleles were first reported worldwide in Chinese individuals. The results of the dual luciferase reporter gene experiment showed that the transcription activity of the mutant-type promoter (HLA-E*01:01:01:06 with "T" allele at nucleotide position-26) was significantly lower compared with the wild-type promoter (HLA-E*01:01:01:01 with "G" allele at nucleotide position-26) (p = 0.0242 < 0.05). HLA-E*01:01:01:06 allele has a protective effect against leukemia through decreasing transcription activity by "T" variation at nucleotide position-26.

Transcriptome analysis of the impact of diabetes as a comorbidity on tuberculosis.

BACKGROUND: Diabetes mellitus patients with pulmonary tuberculosis (DMTB) comorbidity has been recognized as a major obstacle towards achieving the World Health Organization goal of reducing the tuberculosis incidence rate by 90% in 2035. Host immune responses affected by diabetes can lead to increased susceptibility, severity and poor treatment outcomes in DMTB patients, and the underlying mechanisms have not yet been fully elucidated. This study aimed to identify key immunological and cellular components that contribute to increased morbidity and mortality in DMTB cases. METHODS: We performed RNA-Seq of total RNA isolated from peripheral blood mononuclear cells from 3 TB, 3 diabetes mellitus, and 3 DMTB patients and healthy controls, and analyzed differential expression, pathway enrichment and clustering of differentially-expressed genes (DEGs) to identify biological pathways altered specifically in DMTB patients. RESULTS: Bioinformatic analysis of DEGs suggested that enhanced inflammatory responses, small GTPases, the protein kinase C signaling pathway, hemostasis and the cell cycle pathway are likely implicated in the pathogenesis of the DMTB comorbidity. CONCLUSION: The DMTB comorbidity is associated with an altered transcriptome and changes in various biological pathways. Our study provides new insights on the pathological mechanism that may aid the development of host-directed therapies for this increasingly prevalent disease in high TB burden countries.

[Plasma proteomic analysis of diabetes improvement by vitamin D supplementation].

OBJECTIVE: To analyze the effect of vitamin D supplementation on the improvement of diabetes mellitus based on plasma proteomics. METHODS: Five-week-old SPF spontaneously obese rats with type 2 diabetes were randomly divided into a diabetic group and a diabetic vitamin D intervention group, and the control group was Zucker lean rats. The fasting blood glucose of the rats in each group was compared with that of the diabetic vitamin D group, and the plasma proteins of the rats in each group were compared by quantitative analysis of the high-resolution mass spectrometry system iTRAQ, and KEGG signaling pathway analysis was performed. RESULTS: The fasting blood glucose of rats in the diabetic vitamin D intervention group was significantly lower than that of the diabetic group, and the proteins that were differentially expressed in the diabetic vitamin D intervention group were significantly improved. KEGG signaling pathway analysis revealed that the differential proteins in the diabetic group were mainly distributed among enzymes, exosomal proteins, and peptidases and inhibitors, and that the number of differences in these three classes of proteins was significantly reduced in the diabetic intervention group. CONCLUSION: Vitamin D supplementation can improve the differential expression of fasting glucose and plasma proteins in the diabetic rats.

Association between CASC16 rs4784227 polymorphism and breast cancer susceptibility: A meta-analysis.

OBJECTIVE: To explore whether rs4784227 polymorphism of CASC16 is correlated with risk of breast cancer. METHODS: Relevant studies up to December 24, 2020 were searched in PubMed, Embase, Web of Science, CNKI, VIP, and WANFANG databases. Data were analyzed by using Stata 12.0. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and country-based subgroup analyses were conducted. Sensitivity analysis was conducted to assess the stability of the results. Publication bias was assessed by using the Egger regression asymmetry test and visualization of funnel plots. RESULTS: Seven case-control studies enrolling 4055 breast cancer cases and 4229 controls were included. rs4784227 was found significantly associated with increased risk of breast cancer in a dominant (OR = 1.301, 95% CI = 1.190-1.423, P < .001), a recessive (OR = 1.431, 95% CI = 1.216-1.685, P < .001), and an allele model (OR = 1.257, 95% CI = 1.172-1.348, P < .001), while an over-dominant model showed that rs4784227 was correlated with decreased breast cancer risk (OR = 0.852, 95% CI = 0.778-0.933, P = .001). CONCLUSION: The rs4784227 polymorphism of CASC16 gene is correlated with breast cancer susceptibility.

Adaptive Admixture of HLA Class I Allotypes Enhanced Genetically Determined Strength of Natural Killer Cells in East Asians.

Human natural killer (NK) cells are essential for controlling infection, cancer, and fetal development. NK cell functions are modulated by interactions between polymorphic inhibitory killer cell immunoglobulin-like receptors (KIR) and polymorphic HLA-A, -B, and -C ligands expressed on tissue cells. All HLA-C alleles encode a KIR ligand and contribute to reproduction and immunity. In contrast, only some HLA-A and -B alleles encode KIR ligands and they focus on immunity. By high-resolution analysis of KIR and HLA-A, -B, and -C genes, we show that the Chinese Southern Han (CHS) are significantly enriched for interactions between inhibitory KIR and HLA-A and -B. This enrichment has had substantial input through population admixture with neighboring populations, who contributed HLA class I haplotypes expressing the KIR ligands B*46:01 and B*58:01, which subsequently rose to high frequency by natural selection. Consequently, over 80% of Southern Han HLA haplotypes encode more than one KIR ligand. Complementing the high number of KIR ligands, the CHS KIR locus combines a high frequency of genes expressing potent inhibitory KIR, with a low frequency of those expressing activating KIR. The Southern Han centromeric KIR region encodes strong, conserved, inhibitory HLA-C-specific receptors, and the telomeric region provides a high number and diversity of inhibitory HLA-A and -B-specific receptors. In all these characteristics, the CHS represent other East Asians, whose NK cell repertoires are thus enhanced in quantity, diversity, and effector strength, likely augmenting resistance to endemic viral infections.

Associations between Vascular Endothelial Growth Factor Gene Polymorphisms and Different Types of Diabetic Retinopathy Susceptibility: A Systematic Review and Meta-Analysis.

BACKGROUND: Vascular endothelial growth factor (VEGF) gene polymorphisms have been shown to be associated with the risk of diabetic retinopathy (DR), but the results were inconsistent. The aim of this study was to systematically assess the associations between VEGF gene polymorphisms and different types of DR (nonproliferative DR and proliferative DR). METHODS: Electronic databases PubMed, Embase, Web of Science, CNKI, and WANFANG DATA were searched for articles on the associations between VEGF gene polymorphisms and different types of DR up to November 6, 2019. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and subgroup analyses were conducted by ethnicity. Sensitivity analysis was conducted to assess the stability of the results. Publication bias was assessed by using the Egger regression asymmetry test and visualization of funnel plots. A systematic review was conducted for polymorphisms with a high degree of heterogeneity (I 2 > 75%) or studied in only one study. RESULTS: A total of 13 and 18 studies analyzed the associations between VEGF SNPs and nonproliferative DR (NPDR) as well as proliferative DR (PDR), respectively. There were significant associations between rs2010963 and NPDR in Asian (dominant model: OR = 1.29, 95%CI = 1.04 - 1.60); and rs2010963 is associated with PDR in total population (dominant model: OR = 1.20, 95%CI = 1.03 - 1.41), either Asian (recessive model: OR = 1.57, 95%CI = 1.04 - 2.35) or Caucasian (recessive model: OR = 1.83, 95%CI = 1.28 - 2.63). Rs833061 is associated with PDR in Asian (recessive model: OR = 1.58, 95%CI = 1.11 - 2.26). Rs699947 is associated with NPDR in the total population (dominant model: OR = 2.04, 95%CI = 1.30 - 3.21) and associated with PDR in Asian (dominant model: OR = 1.72, 95%CI = 1.05 - 2.84). CONCLUSIONS: Rs2010963, rs833061, and rs699947 are associated with NPDR or PDR, which may be involved in the occurrence and development of DR.

Targeting translation regulators improves cancer therapy.

Deregulation of protein synthesis may be involved in multiple aspects of cancer, such as gene expression, signal transduction and drive specific cell biological responses, resulting in promoting cancer growth, invasion and metastasis. Study the molecular mechanisms about translational control may help us to find more effective anti-cancer drugs and develop novel therapeutic opportunities. Recently, the researchers had focused on targeting translational machinery to overcome cancer, and various small molecular inhibitors targeting translation factors or pathways have been tested in clinical trials and exhibited improving outcomes in several cancer types. There is no doubt that an insight into the class of translation regulation protein would provide new target for pharmacologic intervention and further provide opportunities to develop novel anti-tumor therapeutic interventions. In this review, we summarized the developments of translational control in cancer survival and progression et al, and highlighted the therapeutic approach targeted translation regulation to overcome the cancer.

DNA sequence analysis and Jk blood group genotype-phenotype assessment.

BACKGROUND: The Kidd (JK) blood group is critical for clinical blood transfusion. Various methods for Jk typing have been commonly used, including urea hemolysis, serological test, and genotyping. However, the application of molecular methods has so far been restricted to selected samples and not been applied to the population-scale analysis. METHODS: One hundred eighty-three blood samples, containing 174 samples collected from voluntary blood donors of Chinese Han individuals, together with 3 Jk (aw+b-) and 6 Jk (a-b-) samples, were investigated by standard serology urea hemolysis test and Sanger-sequencing. Complete coverage of exons 4-11 and intron-exon borders have been sequenced. RESULTS: We report the frequencies of three SNPs in exon 4, 7, and intron 9. Besides, sequence analysis revealed the simultaneous DNA variants of intron 7 (-68) and exon 9 (838) found in all samples, suggesting the co-inheritance of these SNPs-taking the observed SNPs frequencies into account. Further, we discuss the potential of the sequencing technique for high-resolution genotyping. CONCLUSIONS: The described sequencing method for Jk exons delivers a genotyping technique for Jk molecular characterization. According to the co-inheritance of these DNA variants in intron 7 (-68) and exon 9 (838), and their regularity linkage with Jk phenotypes, these two sites offer a potential sequencing target for rapid and far more simplified Jk typing that can supplement routine serology and urea hemolysis tests.

[Genotyping of Duffy Blood Group by Microchip Capillary Electrophoresis].

OBJECTIVE: To explore a method for rapidly screening the Duffy blood group genotypes and to establish an information bank of rare blood type donors. METHODS: The microfluidic capillary electrophoresis system and PCR-SSP method were used to analyze the Duffy genotype of 3 936 unrelated O-type blood donors in our center from December 2014 to September 2018. The serologic identification and typing of other blood type system phenotypes for FYa-negative specimen were performed. The Fy (a-b-) specimen was sequenced for genotyping. RESULTS: The phenotypes of FYa-negative specimens were consistent with the genotyping results of the microfluidic capillary electrophoresis system. The results of Duffy phenotyping in 3 936 specimens were follows: Fy (a+b-) 3 564 (90.54%), Fy(a+b+) 353 (8.97%), Fy(a-b+) 18 (0.46%), Fy (a-b-) 1 (0.03%). The gene frequency was FY*A (95.03%), FY*B (4.94%), and FY*Null (0.03%). The bank of rare blood types of 19 FYa-negative specimens was established. CONCLUSION: Microfluidic capillary electrophoresis system is suitable for Duffy blood group genotyping screening. It can be used to establish a bank of rare blood type, so as to solve the problem of urgent blood transfusion in patients with rare blood type, and to improve blood transfusion safety.

Comprehensive analysis of hepatitis B virus infections in blood donors in southern China that are surface antigen positive but nucleic acid testing negative.

BACKGROUND: Hepatitis B virus (HBV) infection is one of the major concerns for the safety of blood transfusion in high-prevalent countries such as in China. Prior studies outside of China have shown hepatitis B surface antigen (HBsAg) false-reactive rate of 0.02% to 0.04%. Similarly, false-negative HBsAg and HBV DNA results may occur in infected donors. Our study analyzed HBsAg enzyme-linked immunosorbent assay (ELISA)-reactive but NAT-negative donations in Shenzhen Blood Center, China. STUDY DESIGN AND METHODS: HBsAg ELISA-positive/NAT-negative plasma samples identified from screening 101,025 donations during 2017-2018 were analyzed by molecular and serologic tests including neutralization, chemiluminescence immunoassays, and various HBV DNA amplification assays. Molecular characterizations of HBsAg-positive/NAT-negative samples were determined by quantitative polymerase chain reaction (qPCR) and nested PCR amplification of the basic core and precore promotor regions (295 base pairs) and HBsAg (S) region (496 base pairs). RESULTS: Screening of 101,025 eligible blood donations identified 157 (0.16%, 95% confidence interval, 0.13%-0.18%) HBsAg ELISA-positive/NAT-negative plasma samples; of those, 71 (45.2%) were HBsAg confirmed positive by further HBsAg testing and DNA positive by molecular tests with increased sensitivity. Of the 71, all but one was antibody to hepatitis B core antigen reactive without antibody to hepatitis B surface antigen, yielding one recent (window-period) HBV infection. Of the remaining donations, 80 (51%) were not considered as HBV-infected donors, and 6 (3.8%) were interpreted as indeterminate since HBsAg results were discordant with unconfirmed HBV DNA results. In the 71 confirmed positives, HBsAg levels ranged from 0.05 to 400 IU/mL and HBV DNA from 6 to 2654 IU/mL; however, the correlation between the two was weak (R2 = 0.24). CONCLUSION: Fewer than half of HBsAg ELISA-positive/NAT-negative samples were confirmed as HBsAg positive. Our study demonstrates that in highly HBV-endemic countries, assays with high sensitivity and specificity may be required.

Efficacy of early antiretroviral therapy 36 hours after HIV infection in one blood donor.

BACKGROUND: Discrepancies can occur with the use of clinical human immunodeficiency virus (HIV) diagnostic reagents for the HIV window period (WP; time from RNA to antibody detection by diagnostic or blood screening assays). Antiretroviral therapy (ART) during acute HIV infection can impact HIV-specific antibodies, antigens, and DNA/RNA detection. In this study, an HIV WP blood donor who initiated ART was monitored, evaluating the immunological and nucleic acid testing (NAT) results for early ART and discussing the potential effects on blood safety. STUDY DESIGN AND METHODS: This was a follow-up study of a HIV WP donor detected 36 hours after high-risk sexual behavior, who was subsequently treated with ART. Immunological and NAT methods were comparatively analyzed. RESULTS: The 4th generation HIV serologic assays were positive at Day 11, and the 3rd generation domestic anti-HIV assay was positive at Day 33. Individual donation (ID) NAT and minipool (MP) NAT of six samples were reactive, but 12-sample MP-NAT was nonreactive. ART resulted in a slow decline of HIV RNA, but HIV DNA was still detected on Day 757. CONCLUSION: After ART, ID-NAT was more sensitive than MP-NAT or serologic detection; however, HIV DNA detection was more sensitive, with DNA but not RNA persistently detectable.