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Genetical Study of Mutation in Maternal-fetal ABO Incompatibility

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2015年第2期35卷 309-315页

作者：余忠清胡锋兰程琼郝建华张建华林雪娜郑宝法萍萍余素燕胡丽华 Department of Blood Transfusion Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of Blood Transfusion Shenzhen Nan Shan Hospital

This study looked into a family involving a rare mother-child ABO blood type inconsistency and explored its genetic and molecular basis. In the family, the mother had type AB blood and the father was blood type B and they gave birth to a baby of blood type O. Their blood types were phenotypically identified by using different techniques, including micro-column gel test, immune inhibition test, absorption and elution tests. The sequences of all 7 exons of ABO allele from the core family members were determined by using PCR and clone-based sequencing. The loci of mutated gene were compared against normal human genes. The result showed that the mother＇s erythrocytes were agglutinable with monoclonal anti-A antibody（2＋） and had agglutination reaction with anti-B antibody（4＋）. The mother＇s serum registered agglutination action with standard blood type A cells. The findings showed an ABO inconsistency. When domestic antibodies were used, the mother＇s erythrocytes yielded agglutination reaction with humanized anti-B serum（4＋） and anti-B monoclonal antibody but were non-agglutinable with humanized anti-A serum and anti-A monoclonal antibody. Upon absorption and elution, the titer of anit-A antibody was 128 both before and after the absorption test, with no significant difference found between pre- and post-absorption values. Our results confirmed that the mother＇s allelic gene was type B and contained type A. The father＇s blood type was type B, and son＇s blood type was type O. Clone-based sequencing revealed that the mother carried a heterozygous gene of B101.01（nt A640→G）/O01, which contained an M214→V mutation that could express a weak expression of antigen A, resulting in blood type AB. However, their son did not have the M214→V mutation, which yielded a false ABO-inconsistency between him and his mother. We were led to conclude that type B gene with a M214→V mutation can encode both antigen B and weak antigen B that can lead to false ABO-inconsistencies.

关键词： mother ABO father sequencing monoclonal Mutation contained false registered clone

Calcineurin in development and disease

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Genes & Diseases 2022年第4期9卷 915-927页

作者： Lei Chen Min Song Chunyan Yao Department of Blood Transfusion First Affiliated HospitalThe Third Military Medical University(Army Medical University)Chongqing 400038PR China

Calcineurin (CaN) is a unique calcium (Ca2+) and calmodulin (CaM)-dependent serine/threonine phosphatase that becomes activated in the presence of increased intracellular Ca2+ level. CaN then functions to dephosphorylate target substrates including various transcription factors, receptors, and channels. Once activated, the CaN signaling pathway participates in the development of multiple organs as well as the onset and progression of various diseases via regulation of different cellular processes. Here, we review current literature regarding the structural and functional properties of CaN, highlighting its crucial role in the development and pathogenesis of immune system disorders, neurodegenerative diseases, kidney disease, cardiomyopathy and cancer.

关键词： Calcineurin Cancer Cardiomyopathy Development Immune system disease Kidney disease Neurodegeneration

ADAMTS13 and von Willebrand factor are useful biomarkers for sorafenib treatment efficiency in patients with hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2019年第5期11卷 424-435页

作者： Hiroaki Takaya Tadashi Namisaki Naotaka Shimozato Kosuke Kaji Mitsuteru Kitade Kei Moriya Shinya Sato Hideto Kawaratani Takemi Akahane Masanori Matsumoto Hitoshi Yoshiji Third department of Internal Medicine Nara Medical University Department of Blood Transfusion Medicine Nara Medical University

BACKGROUND Many advanced hepatocellular carcinoma(HCC) patients are receiving sorafenib treatment. Sorafenib reportedly improves overall survival(OS) significantly in patients with HCC. Prediction of sorafenib response and prognosis in patients with HCC receiving sorafenib treatment are important due to the potentially serious side effects of sorafenib. A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13(ADAMTS13) and von Willebrand factor(VWF) are associated with the pathophysiology of liver cirrhosis and HCC through their roles in hypercoagulability; they are also associated with angiogenesis via vascular endothelial growth factor(VEGF). The imbalance between ADAMTS13 and VWF was associated with prognosis of various cancers in patients undergoing chemotherapy.AIM To investigate ADAMTS13 and VWF as potential biomarkers for sorafenib response and prognosis in patients with HCC receiving sorafenib treatment.METHODS Forty-one patients with HCC receiving sorafenib treatment were included in this study. The initial daily sorafenib dose was 400 mg in all patients. ADAMTS13 activity(ADAMTS13:AC), VWF antigen(VWF:Ag), VEGF levels were determined by enzyme-linked immunosorbent assay. Univariate andmultivariate analyses were used to determine predictive factors for sorafenib response and prognosis in patients with HCC receiving sorafenib treatment.RESULTS ADAMTS13:AC was significantly higher in patients with stable disease(SD),partial response(PR), and complete response(CR) than in those with progressive disease(PD)(P < 0.05). In contrast, VWF:Ag and the VWF:Ag/ADAMTS13:AC ratio were significantly lower in patients with SD, PR, and CR than in those with PD(P < 0.05 for both). Multivariate analysis showed that the VWF:Ag/ADAMTS13:AC ratio was the only predictive factor for sorafenib response and ADAMTS13:AC was the only prognostic factor in patients with HCC receiving sorafenib treatment. The patients with a low ADAMTS13:AC(<78.0) had significantly higher VEGF levels than those with a high ADAMTS1

关键词： ADAMTS13 Von Willebrand factor Biomarkers Hepatocellular carcinoma Sorafenib

Genetic screening of 5 blood group systems of Li ethnic group in Hainan province and establishment of rare blood group bank

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Journal of Hainan Medical University 2022年第20期28卷 6-12页

作者： FU Xiao-ling CAI Xing-quan XIA Lan Department of Blood Transfusion Hainan Women and Children’s Medical CenterHaikou 570311China Department of Blood Transfusion Hainan General HospitalHaikou 570311China

Objective:To screen the blood group system genes of Duffy,Lutheran,Kidd,Diego,Dombrock blood group systems of Li ethnic group in Hainan Province and provide laboratory data for the rare blood group database in this area.Methods:The alleles of Duffy,Lutheran,Kidd,Diego,Dombrock blood group systems of 300 voluntary participants of Li ethnic group in Hainan were detected by sequence-specific primer polymerase chain reaction,and the polymorphism was analyzed.Results:The allele frequencies of Duffy,Lutheran,Kidd,Diego,Dombrock blood group systems of Li ethnic groups in Hainan Province are 0.9583 for Fy^(a),0.0417 for Fy^(b),0.8350 for Au^(a),0.1650 for Au^(b),0.4500 for Jk^(a),0.5500 for Jk^(b),0.0667 for Di^(a),0.9333 for Di^(b),0.1017 for Doa and 0.8983 for Dob,respectively.The antigen incompatibility rates of Fy^(a)/Fy^(b),Au^(a)/Au^(b),Jk^(a)/Jk^(b),Di^(a)/Di^(b),Doa/Dob of Duffy,Lutheran,Kidd,Diego,Dombrock blood group systems were 7.67%,23.76%,37.25%,11.67%and 16.60%,respectively.Conclusion:The gene frequencies of Duffy,Lutheran,Kidd,Diego,Dombrock blood group systems of Li ethnic group in Hainan Province are polymorphic,and the antigen incompatibility rates of alleles are higher,which is quite different from that of other nationalities in China and with unique ethnic distribution characteristics.It is of great significance to establish the rare blood group database in this region.

关键词： blood group gene Gene frequency Rare blood group bank Li ethnic

Human cord blood-derived viral pathogens as the potential threats to the hematopoietic stem cell transplantation safety:A mini review

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World Journal of Stem Cells 2019年第2期11卷 73-83页

作者： Ali Noroozi-aghideh Maryam Kheirandish department of Hematology Faculty of Paramedicine Aja University of Medical Sciences Immunology department Blood Transfusion Research Center High Institute for Research and Education in Transfusion Medicine(IBTO)

Umbilical cord blood(UCB) is a valuable source of hematopoietic stem cells(HSCs) and potential alternative for bone marrow transplantation for patients who lack human leukocyte antigen(HLA)-matched donors. The main practical advantages of UCB over other HSC sources are the immediate availability, lower incidence of graft-versus-host disease, minimal risk to the donor, and lower requirement for HLA compatibility. However, the use of UCB is limited by delayed engraftment and poor immune reconstitution, leading to a high rate of infection-related mortality. Therefore, severe infectious complications, especially due to viral pathogens remain the leading cause of morbidity and mortality during the post-UCB transplantation(UCBT) period. In this context, careful screening and excluding the viral-contaminated UCB units might be an effective policy to reduce the rate of UCBT-related infection and mortality. Taken together,complete prevention of the transmission of donor-derived viral pathogens in stem cell transplantation is not possible. However, having the knowledge of the transmission route and prevalence of viruses will improve the safety of transplantation. To the best of our knowledge, there are few studies that focused on the risk of virus transmission through the UCB transplant compared to other HSC sources. This review summarizes the general aspects concerning the prevalence, characteristics, and risk factors of viral infections with a focus on the impact of viral pathogens on cord blood transplantation safety.

关键词： Cord blood Transplantation safety Viral pathogens

Effects of Perinatal Complications on Coagulation Function in Pregnant Women

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Reproductive and Developmental Medicine 2019年第1期3卷 60-62页

作者： Wei-Qin Yu Xiao-Yan Liu Pei-Min Mao Department of Blood Transfusion Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China

Objectives:To investigate the effects of various complications on the coagulation function of perinatal women.Methods:A total of 210 pregnant women between November 2016 and June 2017 were recruited.The coagulation function indexes,including prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(FIB),and thrombin time(TT),were evaluated in pregnant women with group B Streptococcus(GBS),positive nonstress test(NST),scarred uterus,prenatal fever,macrosomia,gestational hypertension,gestational diabetes,premature rupture of membranes(PROMs),threatened abortion,and oligohydramnios.Results:No significant differences were found in PT,APTT,FIB,and TT in pregnant women with GBS,positive NST,scarred uterus,macrosomia,gestational hypertension,gestational diabetes,PROMs,and oligohydramnios.Moreover,significantly decreased PT and APTT and significantly increased TT were found in pregnant women with prenatal fever compared to normal controls,whereas significantly increased TT was also observed in those with threatened abortion.Conclusions:Among the complications that occur in pregnant women,prenatal fever and threatened abortion have important effects on coagulation function.

关键词： Coagulation Complication Perinatal Period Pregnancy Prenatal Fever Threatened Abortion

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乌骨藤提取物对人红细胞的毒性研究（英文）

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2017年第7期18卷 597-604页

作者： Ke HAO Bing-yu CHEN Kai-qiang LI Yu ZHANG Cai-xia LI Ying WANG Lu-xi JIANG Jiang SHEN Xiang-chai GUO Wei ZHANG Meng-hua ZHU Zhen WANG Research Center of blood transfusion Medicine Ministry of Education Key Laboratory of Laboratory Medicine Department of Blood Transfusion Zhejiang Provincial People's Hospital People's Hospital of Hangzhou Medical College Department of Blood Transfusion Lishui People's Hospital

目的:评估乌骨藤提取物对红细胞形态及生理功能的影响,并初步探讨其作用机制。创新点:首次检测乌骨藤提取物对红细胞的毒性作用,并且初步探索此毒性作用与乌骨藤导致的红细胞内活性氧(ROS)和钙离子水平的相关性。方法:不同浓度乌骨藤提... 详细信息

目的:评估乌骨藤提取物对红细胞形态及生理功能的影响,并初步探讨其作用机制。创新点:首次检测乌骨藤提取物对红细胞的毒性作用,并且初步探索此毒性作用与乌骨藤导致的红细胞内活性氧(ROS)和钙离子水平的相关性。方法:不同浓度乌骨藤提取物(0、64、128和256μg/ml)处理红细胞24 h,通过流式细胞术检测前向角散射(FSC)和侧向角散射(SSC),计算红细胞破碎率和大小改变,通过显微镜观察形态学的变化;装载2',7'-二氯荧光黄双乙酸盐(DCFH-DA)和钙荧光探针Fluo-4染料,通过流式细胞术分别检测红细胞ROS和钙离子荧光强度的变化;通过观察一系列低渗生理盐水下红细胞的溶胀情况,评估乌骨藤提取物对红细胞脆性的改变。结论:乌骨藤提取物剂量依赖性地增加红细胞的破碎率(图1),导致FSC增加(图2),同时高浓度乌骨藤提取物(256μg/ml)导致红细胞圆盘状结构消失(图3);128和256μg/ml乌骨藤提取物处理红细胞导致胞内钙离子显著增加(图4);乌骨藤提取物在高糖环境中诱导红细胞ROS累计,并最终导致红细胞脆性增加(图5)。上述结果显示,乌骨藤提取物对红细胞有毒性作用,并有可能在临床抗癌治疗中破坏红细胞引起潜在的毒副作用(图6)。

关键词：乌骨藤提取物红细胞钙离子活性氧(ROS) 红细胞脆性

miR-34a mediates oxaliplatin resistance of colorectal cancer cells by inhibiting macroautophagy via transforming growth factor-β/Smad4 pathway

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World Journal of Gastroenterology 2017年第10期23卷 1816-1827页

作者： Chen Sun Fu-Jing Wang Hao-Gang Zhang Xun-Zheng Xu Rui-Chun Jia Lei Yao Peng-Fei Qiao department of General Surgery the Second Affiliated Hospital of Harbin Medical University Department of Blood Transfusion the Second Affiliated Hospital of Harbin Medical University

AIM To investigate whether micro RNA(mi R)-34 a mediates oxaliplatin(OXA) resistance of colorectal cancer(CRC) cells by inhibiting macroautophagy via the transforming growth factor(TGF)-β/Smad4 pathway.METHODS miR-34 a expression levels were detected in CRC tissues and CRC cell lines by quantitative real-time polymerase chain reaction. Computational search, functional luciferase assay and western blotting were used to demonstrate the downstream target of miR-34 a in CRC cells. Cell viability was measured with Cell Counting Kit-8. Apoptosis and macroautophagy of CRC cells were analyzed by flow cytometry and transmission electron microscopy, and expression of beclin I and LC3-II was detected by western blotting.RESULTS Expression of miR-34 a was significantly reduced while expression of TGF-β and Smad4 was increased in CRC patients treated with OXA-based chemotherapy. OXA treatment also resulted in decreased mi R-34 a levels and increased TGF-β and Smad4 levels in both parental cells and the OXA-resistant CRC cells. Activation of macroautophagy contributed to OXA resistance in CRC cells. Expression levels of Smad4 and miR-34 a in CRC patients had a significant inverse correlation and overexpressing mi R-34 a inhibited macroautophagy activation by directly targeting Smad4 through the TGF-β/Smad4 pathway. OXA-induced downregulation of miR-34 a and increased drug resistance by activating macroautophagy in CRC cells.CONCLUSION miR-34 a mediates OXA resistance of CRC by inhibiting macroautophagy via the TGF-β/Smad4 pathway.

关键词： miR-34a Oxaliplatin Colorectal 癌症 Macroautophagy 转变生长 factor-/Smad 小径

Recombinant human erythropoietin accelerated the proliferation of non-small cell lung cancer cell lines and reduced the expression of VEGF,HIF-1α,and PD-L1 under a simulated hypoxic environment in vitro

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Chronic Diseases and Translational Medicine 2022年第2期8卷 124-133页

作者： Yajing Zhang Yangchun Feng Xiaojie Sun department of Laboratory Affiliated Cancer Hospital of Xinjiang Medical UniversityUrumqiXinjiang 830011China Department of Blood Transfusion Affiliated Cancer Hospital of Xinjiang Medical UniversityUrumqiXinjiang 830011China

Background:As erythropoietin(EPO)has been used to treat anemia in cancer patients,negative controversy has continued.Unfortunately,its effects on non-small-cell lung carcinoma(NSCLC)cell lines are uncertain and the phenomenon of inducing immune escape of tumor cells remains to be explored.This study aimed to provide an important basis for the application of exogenous EPO in the treatment of tumor-associated anemia.Methods:Cells were cultured in 1%O2,5%CO_(2),and 94%N2 to simulate a hypoxic environment of the tumor.A549 cell line(lower expression EPOR)and NCI-H838 cell line(higher expression EPOR)were treated with 2 and 8 U/ml recombinant human EPO(rhEPO).CCK-8 method was used to determine the logarithmic growth phase of the cells and to detect cell proliferation.The expression levels of VEGF,HIF-1α,and PD-L1 were determined by western blot.One-way ANOVA was used for statistical analysis between groups,withp<0.05 indicating a significant difference.Results:Hypoxia itself could decrease the survival rate of NSCLC cells.Under the hypoxic condition,rhEPO induced tumor cells proliferation,especially in the NCI-H838 cell line,where 2 U/ml rhEPO increased the total number of surviving cells(Hypoxia+rhEPO 2 U/ml vs.Hypoxia,p<0.05).Western blot analysis showed that hypoxia upregulated the expression of VEGF,HIF-1α,and PD-L1 in NSCLC cell lines(Normoxia vs.Hypoxia,p<0.05),but may not be dependent on the expression levels of EPOR.RhEPO decreased the expression levels of VEGF and HIF-1α.In the A549 cell line,it depended on the concentration of rhEPO and was particularly obvious in HIF-1α(Hypoxia vs.Hypoxia+rhEPO 2 U/ml vs.Hypoxia+rhEPO 8 U/ml,p<0.05).A low concentration of rhEPO may not reduce VEGF expression.In the NCI-H838 cell line,the effect of rhEPO on VEGF was more obvious,but it may be independent of rhEPO concentrations.The downregulation of PD-L1 expression by rhEPO was only presented in the A549 cell line and required higher rhEPO concentrations(Hypoxia+rhEPO 8 U/ml vs.Hypoxia&Hypoxia+rhEPO 2 U/ml,p<0.05).Conclusio

关键词： cell proliferation hypoxia hypoxia-inducible factor 1 non-small cell lung cancer vascular endothelial growth factor