Using experimental results of international proficiency testing for establishing the decision limit value of mean fluorescent intensity of anti-human leukocyte antigen antibody and its clinical application / 中华器官移植杂志

Objective:Establish the decision threshold value of mean fluorescence intensity of anti-human leukocyte antigen(HLA)antibody through statistical analyzing the results of international proficiency testing(PT)organized by American Society for Histocompatibility and Immunogenetics(ASHI).Methods:Single antigen reagent and liquid chip(Luminex)technique were used to detect anti-HLA antibody. A retrospective analysis of the HLA antibody PT results of 55 quality control samples from 11 times organized by ASHI from 2012 to 2019 was reviewed.Results:Among 79 kinds of HLA-I antibodies, 21, 43 and 15 types of HLA-A, B and Cw antibodies were detected respectively, while among 44 kinds of HLA-Ⅱ antibodies, 18, 7 and 19 types of HLA-DRB1, DQB1 and DPB1 antibodies were detected respectively. After analyzing the MFI detection value of different specific antibodies in each PT samples at our laboratory and the coincidence rate of the negative / positive results judged by ASHI through summarizing the results of multicenter participating in the same period, MFI values of HLA antibody were arranged from high to low into the intervals of possible saturation value, positive decision value, positive judgment threshold value, suspicious positive reference value and suspicious negative reference value , according to the coincidence rate of 95%, 90%, 80%, 79%~50% and <50%.Thus, the decision limit value table of HLA specific antibody at our laboratory was established. And 42 kinds of HLA antibody types were detected with complete data.When the MFI values of various HLA-I or HLA-Ⅱ antibodies are found to be 80% or more in the table, it can be used to judge the detection of HLA antibodies. When HLA antibody MFI value reaches the positive decision value, it may have a certain guiding significance for clinical diagnosis and treatment. And when antibody MFI value reaches the saturation value and lies in the suspicious positive or suspicious negative reference threshold, it just suggests that the clinical need for dynamic follow-up of anti-HLA antibody detection.Conclusions:The decision limit value of MFI of laboratory HLA antibody is established based on the international PT experimental results, which is of reference value for the interpretation of experimental results and clinical diagnosis and treatment. A transplant ation center should pay attention to the quality control of comparison test between laboratories in the detection of HLA antibodies.

Clinical significance of HLA-A, -B, -C, -DRB1, -DQB1 haplotype gene frequencies / 中华血液学杂志

Objective@#To analyze family-based haplotype frequencies of HLA-A, -B, -C, -DRB1 and -DQB1 genes and their clinical significance.@*Methods@#The data of HLA genotyping in 3568 families undergoing related haploidentical transplantation between 2012 and 2017 at the First Affiliated Hospital of Soochow University were retrospectively evaluated. The HLA genotyping was performed by PCR amplification with sequence-based typing (PCR-SBT) and sequence-specific oligonucleotide probe (PCR-SSOP) methods. The family genetic analysis and haplotype frequencies were also investigated.@*Results@#All the families were divided into 3 groups, including group1 of 1 422 entire families; group2 of 1 310 patients and either of their parents or one of their children; group3 of 836 patients and their HLA≥5/10 matched sibling donors. In the haplotypes with frequencies greater than 0.1% in group1+ group2, the frequency of A*11∶01-B*40∶01-C*03∶04-DRB1*11∶01-DQB1*03∶01, A*02∶07-B*51∶01-C*14∶02-DRB1*09:01-DQB1*03∶03 were significantly different between group1 and group2 (P=0.029, 0.033) . The frequency of A*11∶01-B*46∶01-C*01∶02∶01G-DRB1*09∶01-DQB1*03∶03 was significantly different between group1 and group3 (P=0.035) . The frequency of A*02∶01-B*40∶01-C*07∶02-DRB1*09∶01-DQB1*03∶03 was significantly different between group1 and group2 (P=0.034) , or group1 and group3 (P=0.034) . The frequency of A*24∶02-B*13∶01-C*03∶04-DRB1*12∶02-DQB1*03:01 was significantly different between group2 and group3 (P=0.046) .@*Conclusion@#In this study, we summarize the prevalence of haplotype frequencies in terms of HLA-A, -B, -C, -DRB1 and-DQB1. Based on the database of family haplotype analysis, patients and donor candidates are sorted with matched HLA genotype while unmatched HLA haplotype. Even in patients without entire family information, HLA haplotype analysis assists in choosing the optimal related or unrelated donors.

New-concept animal vaccines emerging in recent years / 生物工程学报

Animal infectious diseases pose a serious and continuing threat to the animal health and cause huge economic losses throughout the world. Vaccination is one of the most effective solutions to prevent and control animal infectious diseases. With the development of biotechnologies and the need for disease prevention and control, the focus of vaccine research has been shifted to the development of safe, efficient, broad-spectrum, low-dose and marker vaccines. Novel vaccines capable of inducing high levels of both humoral and cellular immune responses are promising to provide more efficient protection against animal infectious diseases. This minireview summarizes the development, applications, advantages and disadvantages of new-concept animal vaccines emerging in recent years, including mucosal vaccines, long-acting and fast-acting vaccines, chimeric vaccines, nanoparticle vaccines, and so on. Furthermore, we discuss future directions of the vaccines, in order to provide new insights for animal vaccine development.

The role of different KIR haplotypes in haplo-identical hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the role of different immunoglobulin- like receptor (KIR)haplotypes in haplo- identical hematopoietic stem cell transplantation (HSCT).</p><p><b>METHOD</b>Killer cell KIR genotyping was performed on 468 individuals from 156 unrelated families by PCR-SSP. A total of 624 KIR haplotypes from the parents were used for haplotype analysis. Ninety-two patients received haplo-identical HSCT from one of the parents.</p><p><b>RESULTS</b>The family study showed segregation of one A haplotype and at least 20 unique B haplotypes. The frequency of haplotype A was 72.92% (455/624). The most commonly observed haplotypes in group B were B1, B2, and B3, present at a frequency of 10.26%, 5.77%, and 4.48%, respectively. Compared to KIR gene matched donors (n=17), grafts from KIR gene mismatched donors (n= 14) had a positive effect on survival after haplo- identical HSCT for AML/MDS patients (OS: 88.2%vs 42.9%,P=0.015; RFS: 88.2%vs 35.7%,P=0.007). No effect was observed for ALL/NHL patients (OS: 76.0%vs 75.0%,P=0.727; RFS: 68.0%vs 65.0%,P=0.866). A significantly lower survival rate was observed for transplants from AA (n=52) and AB1/AB2 donors (n=15), compared to other group Bx donors (n=25) (OS: 53.3%vs 96.0%,P=0.017; RFS: 53.3%vs 92.0%,P=0.019). Meanwhile, the risk of relapse was much higher in AA group (n=52) compared to Bx group (n=40) (25.0%vs 5.0%,P=0.009). A higher risk of TRM was observed in AB1/AB2 group (P=0.012). In addition, transplant from donors carried Cen-B was associated with an increased survival compared with Cen-A homozygous donors (OS: 94.7%vs 68.5%,P=0.036; RFS: 89.5%vs 64.4%,P=0.045).</p><p><b>CONCLUSION</b>Overall, KIR genotyping and haplotype analyses should be useful for selection of the most optimal donors with favorable KIR gene grafts. KIR gene mismatch donors should be preferred for AML/MDS patients. Selecting donors carried Cen- B and avoiding the selection of donors of KIR genotype AA/AB1/AB2 was strongly advisable for haplo-identical HSCT.</p>

Effects of KangAi injection on apoptosis and proliferation of rectal cancer Lovo cells in vitro / 中国基层医药

Objective To investigate the effects of KangAi injection on apoptosis and proliferation of rectal cancer Lovo cells in vitro.Methods SubG1 and Annexin -V /PI were used to examine the apoptosis of Lovo cells in vitro.Real -time PCR was used to examine the expression of Caspase -3 and Bcl -2 at mRNA level.Proliferation protein ki -67 was detected by flow cytometry.Results Lovo cells treated with KangAi injection 180μL/mL for 48h increased apoptosis rate from (4.75 ±1.04)% to (45.61 ±5.22)% with SubG1 (t =7.68,P <0.01 ),and (7.28 ±1.99)% to (57.02 ±3.88)% with Annexin -V /PI(t =11.42,P <0.01).Lovo cells treated with KangAi injection 180μL/mL for 48h increased the expression of Caspase -3 at mRNA level(t =4.06,P <0.05),while Bcl-2 decreased(t =5.69,P <0.01 ).Lovo cells treated with KangAi injection 180μL/mL for 48h decreased the expression of ki -67 from (95.79 ±1.66)% to (65.84 ±4.80)%(t =5.90,P <0.01 ).Conclusion KangAi injection can promote apoptosis and inhibit proliferation of rectal cancer Lovo cells in vitro.

CD1d(hi)CD5⁺ B cells differentiate into antibody-secreting cells under the stimulation with calreticulin fragment

Calreticulin (CRT) is a multifunctional molecule in both intracellular and extracellular environment. We have previously found that a recombinant CRT fragment (rCRT/39-272) could modulate T cell-mediated immunity in mice via activation and expansion of CD1d(hi)CD5⁺ B cells as well as induction of CRT-specific regulatory antibodies. Antibody secreting cells (ASCs) are terminally differentiated B cells responsible for producing antibodies to participate in positive immune response as well as immune regulation. In this study, we demonstrate that rCRT/39-272 differentiates murine CD1d(hi)CD5⁺ B cells into ASCs marked by increased expression of plasma cell-associated transcription factors and production of polyreactive antibodies against DNA and CRT in vitro. Intraperitoneal administration of rCRT/39-272 augmented differentiation of CD1d(hi)CD5⁺ B cells into ASCs in naïve mice or mice with experimental autoimmune encephalomyelitis. Thus, we propose that ASC differentiation and subsequent antibody production of CD1d(hi)CD5⁺ B cells are key steps in CRT-mediated immunoregulation on inflammatory T cell responses.

The efficacy and side effects of exemestane in the treatment of postmenopausal women with bone metastasis of breast cancer / 中国综合临床

Objective To observe the efficacy and side effects of exemestane in postmenopausal breast cancer patients with bone metastasis.Methods One hundred and ten postmenopausal breast cancer patients with bone metastasis were treated with exemestane 25 mg.Results In the evaluable data from 110 patients,the complete remission(CR)was encountered in 7 cases,partial remission(PR)in 28 cases,with a total response rate of 31.8％ ;Thirty nine patients had stabled diseases for more than 24 weeks.It produced a clinical benefit (CR + PR + SD)over 24 weeks in 74 cases(67.3％).Diseases progressed in 12 of the cases(10.9％).The patients with positive ER and PR status had a higher chance to be benefited from the treatment than those with negative receptor status.The clinical efficacy was not correlated with treatment history,pathological subtypes and bone,liver,lung and lymph node metastasis(x2 =0.045,0.078,0.200,P ＞ 0.05).No severe adverse effects were observed.Conclusion Exemestane is effective to treat bone metastasis of breast cancer with minor adverse reactions and good tolerability.

Relationship and expression of survivin and p53 in colorectal carcinoma / 中国基层医药

Objective To investgate the expression of survivin and p53 and to evaluate their relationship in colorectal carcinoma.Methods The expression of survivin and p53 were evaluted using immunohistochemistry in 58 cases of colorectal carcinoma tissue,25 cKses of paracarcinoma tissue and 39 cases of normal colonia membrance tissue.Results The positive rates of survivin and p53 in colorectal carcinoma were 72.4%(4:2/58)and 63.8%(37/58).The positive rates of survivin and p53 in colorectal carcinoma were significantly higher than paracarcinoma tissue and normal colonia membrance tissue(P＜0.05).Survivin and p53 expression were related to metastasis of colorectal carcinoma(P＜0.05).The expression of survivin was obviously correlated with p53 in colorectal carcinoma(r=0.291,P=0.020).Conclusion Overexpreasion of survivin may play a crucial role in the origin and development of colorectal carcinoma.