Abstract: Waldenström macroglobulinemia (WM) is a low-grade lymphoplasmacytic lymphoma of mature IgM+ B-lymphocytes that remains incurable despite recent practice-altering therapeutic advances and refinements in patient care. Defining features of WM include symptoms that can either be attributed to the extent and site of tissue infiltration by tumor cells or the magnitude and immunological specificity of the monoclonal serum IgM (paraprotein). Current guidelines for the therapeutic stratification of patients with newly diagnosed WM recommend BR (bendamustin-rituximab) for bulky and/or symptomatic disease. DRC (dexamethasone-rituximab-cyclophosphamide) is a good treatment option for relapsed or refractory WM. Ibrutinib – a small-drug inhibitor of Bruton tyrosine kinase, approved for WM treatment in the United States and Europe in 2015 – is particularly effective for tumors that harbor the hallmark MYD88L265P mutation. Plasma exchange is indicated in patients with IgM-dependent hyperviscosity syndrome. The potential development of novel drugs and combination regimens generates promise that the future of patients with WM is bright.
Abstract: DNA based blood group genotyping has been widely used in clinical blood transfusions, and a number of different molecular blood group testing methods have been developed, including the detection of single nucleotide polymorphism (SNP) and genomic DNA sequencing. As the molecular bases of blood groups can differ widely between ethnic groups, a set of reference DNAs, especially for the Chinese population, is required for the development and validation of these methods, and for their optimal use in routine practice in China. In this study, a total of 100 DNA samples obtained from 60 established cell lines and 40 Chinese blood donors were typed for 31 red blood cell antigens of 13 blood group systems using a multiplex polymerase chain reaction (PCR) assay. Finally, nine DNA samples were selected to establish a panel of reference DNA that included M, N, S, s, Mur, Lua, Lub, Aua, Aub, K, k, Fya, Fyb, Jka, Jkb, Dia, Dib, Sc1, Sc2, Doa, Dob, Coa, Cob, Kna, Knb, Inb, Vel antigens and Fy (a-b-) null phenotype.
Abstract: Activation-induced cytidine deaminase (AID), an essential enzymatic activity required for somatic hypermutation and immunoglobulin class switch recombination in the course of normal B-lymphocyte development, has been implicated in the initiation and promotion of malignant B-cell tumors by virtue of a complex mechanism that includes the generation of oncogene-activating genomic rearrangements and the introduction of point mutations in cancer genes. Here, we use transgenic mouse models of B-cell lymphoma driven by the pro-inflammatory cytokine, interleukin 6 (IL-6), or the survival-enhancing oncoprotein, B-cell leukemia 2 (BCL-2), to evaluate the impact of loss of AID on neoplastic B-cell development. We show that AID deficiency accelerates BCL-2 induced lymphoma but delays IL-6 induced lymphoma. This led us to conclude that AID may function as tumor suppressor or tumor promoter, depending on the genetic context. Elucidating the mechanism of AID's dual function during malignant B-cell transformation may be important for new approaches to tumor treatment and prevention.
Abstract: Two common polymorphisms of 588G/A and 838G/A have been demonstrated in the JK gene, and the latter defines the Jka/Jkb phenotypes. The Jknull phenotype has been characterized as the absence of Jka and Jkb antigen expression on red cells. We performed a molecular analysis of a family with the Jknull phenotype and subsequently demonstrated the presence of different JK cDNA haplotypes. In the study, three members of a Jknull family and 48 randomly-selected individuals were enrolled. The coding exons of the JK gene of the Jknull family members were amplified by polymerase chain reaction (PCR), and the sequences were analyzed. The genomic region encompassing exons 7~9 of the JK gene was PCR-amplified, cloned, and sequence-determined to elucidate the JK haplotype. We demonstrated that 3 missense mutations, 222C>A, 499A>G and 896G>A were in the JK genes of the Jknull family members, in addition to the known IVS5–1g>a splice site mutation. Analysis of 48 randomly-selected individuals showed that 499A>G was a common polymorphism, besides 2 Jknull alleles with respective mutation of 222C>A and 896G>A being demonstrated in the Jknull family. After compiling the nucleotide information of the polymorphic 499, 588, and 838 positions from the randomly-selected individuals, 5 JK cDNA haplotypes, constituted by the 3 polymorphic sites, were demonstrated. Among these, the JKa1 (499A, 588G and 838G; 46.9%),JKb1 (499A, 588G and 838A; 23.9%), and JKb2(499G, 588G and 838A; 21.9%) were found as the 3 major haplotypes in the Taiwanese population. In conclusion, the Jknull phenotypes with respective mutations of 222C>A, 896G>A and IVS5–1g>a, were identified in a Taiwanese family. The existence of 5 JK cDNA haplotypes with the 499A/G polymorphism was also demonstrated in the Taiwanese population.
Abstract: Electronic crossmatching is a computer-assisted technology used to confirm if red blood cell (RBC) blood products are suitable for the intended recipient. In addition to mainland China, electronic crossmatching has been used in many countries. Here we have developed an electronic crossmatching system for clinical application. The primary and advanced system of electronic crossmatching was developed, the primary system includes ABO and RhD blood group antigens, and the advanced system includes 18 common RBC group antigens. We completed in-situ and online testing; the system was installed in six general hospitals in Dongguan for clinical application. A total of 31,941 crossmatches were performed by both electronic and serological crossmatching from July 1st, 2015 to April 30th, 2016. The electronic crossmatch shows to be more powerful than serological crossmatching, if RBC blood products and recipients were compatible when electronic and serological crossmatch completed, all blood were issued to clinic. In this condition, no case of hemolytic transfusion adverse reaction occurred. In conclusion, the electronic crossmatch system can be used in transfusion medicine and is capable of reducing laboratory workload and costs, as well as improving transfusion safety.
Abstract: The SLC14A1 gene, which encodes the important Kidd blood group antigens, has not been systematically analyzed at the molecular level in Chinese individuals. In this study, SLC14A1 genetic polymorphism was examined in Chinese individuals with Jk(a+b-), Jk(a+b+), and Jk(a-b+) expression. The Kidd phenotype was determined for 146 specimens using monoclonal anti-Jka and -Jkb antibodies. From these, 87 specimens were Jk(a-b+), 21 were Jk(a+b-), and 38 were Jk(a+b+). According to the Kidd phenotype results, 20 specimens were randomly selected from each group, i.e., Jk(a-b+), Jk(a+b-), and Jk(a+b+), for the molecular analyses of exons 3 to 11 of the SLC14A1 gene. Novel alleles were detected in the SLC14A1 gene, including IVS3-106A, IVS3-99A, exon3 130G, IVS4-299G, IVS4-293G, IVS4+211C, IVS4 +230C, exon6 499A, exon6 588A, IVS7-68T, IVS9+244G, and IVS10-153T, indicating that the locus harbored significant polymorphism. We also showed that IVS4-299, IVS7-68, and IVS10-153 were novel SNPs absolutely associated with exon 8 nt. 838. The minor allele frequencies were all greater than 10% and all SNPs in the Chinese population showed Vel antigen expression on RBC membranes. We identified 12 SNPs in the SLC14A1 gene in the Chinese population, IVS3-106A, IVS3-99A, exon3 130G, IVS4-299G, IVS4-293G, IVS4+211C, IVS4 +230C, exon6 499A, exon6 588A, IVS7-68T, IVS9+244G, and IVS10-153T. Our results also indicated that three novel SNPs produced Jka and Jkb antigens in Chinese individuals.
Abstract: A better understanding of the factors related to cancer helps health professionals like nurses to provide more individualized health care which will affect the prognosis of patients with ovarian cancer The aim of this study was to analyze the association of clinicopathological features and risk factors with ovarian cancer prognosis. This retrospective study recruited 103 patients with ovarian cancer who were treated at a single institution during the period from May 2002 to May 2014. The blood markers CA125, CA153, and serum ferritin (SF) were detected in all patients before surgery. Risk factors were analyzed using univariate and multivariate logistic regression models and survival analyses were performed using Kaplan–Meier. Menopause was considered to be associated with SF expression levels. The expression of CA125, CA153, and SF were associated with metastasis and FIGO stage. The expression of CA153 was associated with tumor grade. FIGO stage, menopause, expression levels of CA125 and CA153 are associated with poor prognosis in ovarian cancer patients. Through what we have found, nurses should pay attention to these prognostic factors in order to provide optimal nursing care and improve the quality of life of patients with ovarian cancer.
Abstract: Diego blood antigens are important antigens in Mongoloid people and native South Americans owing to the Dia positivity rate found in these populations. However, the prevalence of Dia+ is different among native populations of America and China. Our study reviewed the genotype, phenotype, and alloantibody titre of Diego blood group antigens to explain the existence of the dosage effect for Diego antigens. The prevalence of Dia+ varied from 2.26% to 10.43% in the Chinese population was lower than that observed in Native Americans living in USA, Brazil, and Venezuela. The Di(a+b-)/Di(a+b+) ratio in the Chinese was 0.0044~0.0268, which was also lower than that observed in native Americans at 0.0203–0.1628, indicating that the major allele was Di(a+b+) in Dia+Chinese or Asians. We also collected Di(a+b-), Di(a+b+), and Di(a-b+) samples from Chinese samples to examine the agglutinin titres with anti-Dia and anti-Dib and the results supported the existence of the dosage effect for Diego antigens. The agglutinin titres of anti-Dia in Di(a+b+) specimens were lower than those in Di(a+b-) specimens, and agglutinin titres of anti-Dib in Di(a+b+) specimens were lower than those in Di(a-b+) specimens. Alloantibodies against Dia and Dib antigen are majorly responsible for haemolytic disease of the new-born and anti-Dia reactions resulting in stillborn foetus and transfusion reactions, such as fever and rash,were also reported in the Chinese population.
Abstract: Perioperative transfusion has adverse effects in patients undergoing cardiac surgery. The effect of leukocyte-depleted (LD) erythrocyte transfusion in pediatrics’ cardiac surgery was until now unknown. A retrospective cohort study was conducted among pediatric patients who were no more than 3 years old and transfused with red blood cells during an open-heart surgery. Investigations were made into mechanical ventilator treatment duration, length of stay in the intensive care unit (ICU) and 90-day survival. A total of 174 pediatric patients were included in our study. The average age was 21.90 months old and the average weight was 9.18 kg. There were 107 patients received non-leukocyte-depleted (NLD) red blood cell (RBC) transfusion and 67 patients received LD erythrocyte transfusion. No statistically significant differences were detected in the 90-day survival rates between the NLD group and the LD group. Statistically significant differences were detected in the time spent on the mechanical ventilator[(5.3 ± 2.0) d vs. (2.6 ± 1.0) d; P= 0.01] and the lengths of ICU stay [(9.4 ± 6.0) d vs. (5.6 ± 4.0) d; P=0.02] between the NLD group and the LD group. LD blood transfusion was associated with decreased length of stay in ICU and the decreased time on the mechanical ventilator in pediatric cardiac surgery.
Abstract: On the basis of anti-TROP2 Fab antibody, this study seek to construct a eukaryotic expression system of human anti-TROP2 antibody IgG, and to analyse the inhibition function of human anti-TROP2 antibody IgG in the cell proliferation of pancreatic cancer. The heavy and light chain genes of anti-TROP2 antibody were amplified respectively to establish the recombinant expression vector of human anti-TROP2 antibody IgG, named pWS-anti-TROP2. The human anti-TROP2 antibody IgG was obtained through transfecting the plasmids into the CHO dhfr- cell line, selecting the monoclonal cell strains with high amounts of antibody expression by MTX screening and applying Protein G affinity in purification. The identification and immunologic activity of human anti-TROP2 antibody IgG were researched by Western Blot,SDS-PAGE, ELISA, immunofluorescence assay and flow cytometry method (FCM). MTT assay was conducted to analyse the inhibition effect of human anti-TROP2 antibody IgG on BxPC3 cell proliferation. The human anti-TROP2 antibody IgG eukaryotic expression system was established successfully to express human anti-TROP2 antibody IgG, in which the molecular weight of heavy chain and light chain were consistent with expectation, and it could specifically combine with TROP2 protein, the antibody titer reached 1:6,400. The MTT assay results indicated that human anti-TROP2 antibody IgG had a significant effect on inhibiting the proliferation of BxPC3 cell, and the inhibition function can be gradually increased with improved antibody dose and prolonged time. In the study, the human anti-TROP2 antibody IgG eukaryotic expression system was constructed successfully, the antibody could specifically bind to TROP2 protein on the surface of pancreatic cancer cells, and it is shown to have a significant inhibitory action in pancreatic cancer cell proliferation.