1.Differential expression and molecular genetic characteristics of CD36 antigen in platelet donor database in Shaanxi province, China
Tianju WANG ; Jun QI ; Manni WANG ; Yuhui LI ; Lixia SHANG ; Le CHEN ; Xiaofang WANG
Chinese Journal of Blood Transfusion 2025;38(5):621-628
Objective: To screen the frequency of CD36 antigen expression in platelet donor database in Shaanxi province and analyze the molecular genetic characteristics of samples with CD36 antigen deficiency and low expression. Methods: A total of 525 platelet donors samples were randomly collected during May 2023. CD36-FITC monoclonal antibody was used for immunofluorescence labeling, and flow cytometry was applied to detect the expression of CD36 antigen on platelets. For samples with CD36 antigen deficiency on platelets, the expression of CD36 on monocytes was further detected. Samples with CD36 antigen deficiency and low expression were sequenced and analyzed. Results: Among the 525 blood samples, 99.24% (521/525) showed positive expression of CD36 antigen. There were differences in the expression intensity of CD36 antigen, with low expression accounting for 3.43% (18/525) and CD36 antigen deficiency accounting for 0.76% (4/525), all of which were type Ⅱ deficiency. The exon mutation frequency of CD36 type Ⅱ deficiency and low expression samples was 31.82% (7/22), and the exon mutation types were 121-1_126delGCAAGTT, 329-330delAC, 1142T>G, 1204-1246dupl 43bp, 1221G>A, and 1228-1239delATTGTGCCTATT. All four cases of CD36 type Ⅱ deficiency had a 121-6 T>C mutation in intron 3. All CD36 low expression samples had a mutation of 282-10A>G, and 121-6T>C mutation rate was 61.1%(11/18). Conclusion: There were differences in the expression of CD36 antigen in the platelet donor database in Shaanxi province, which may be caused by multiple molecular genetic variations. The frequency of CD36 antigen deficiency in Shaanxi was lower than that of Han, Zhuang and Yao populations in southern China. This study provides references for solving the CD36 antibody mediated transfusion reaction and auxiliary treatment of diseases caused by CD36 antigen deficiency in the future. It also provides a basis for investigating the molecular mechanisms of CD36 deficiency and low expression.
2.Observation of azithromycin sequential therapy combined with pediatric massage on chronic cough after mycoplasma pneumoniae infection in children
Rufang LIU ; Xiaohong LIN ; Yinying PENG ; Manni CHEN ; Lin WEI
China Pharmacist 2024;27(2):309-316
Objective To explore the clinical efficacy of azithromycin sequential therapy(AST)combined with infantile massage(IM)in children with chronic cough after mycoplasma pneumoniae infection(CCAMP)phlegm-heat closed lung syndrome(PHCLS),and provide a new scheme for the clinical diagnosis and treatment of CCAMP.Methods The study retrospectively collected children with CCAMP-PHCLS diagnosed in the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from March 2022 to March 2023.According to the treatment regimes,the children were divided into AST group and AST+IM group.The differences in cough symptoms integral and inflammatory factors(IL-6,PCT and CRP)between the two groups of CCAMP-PHCLS children were observed and compared.In addition,the total time to disappearance of clinical symptoms/signs,negative conversion of serum MP antibody(MP-IgM),total treatment response rate and incidence of adverse reactions were compared between the two groups.Results A total of 98 CCAMP-PHCLS children were collected,49 in each group.There were no significant differences between the AST+IM group and AST group in daytime cough symptoms points,nighttime cough symptoms points,serum IL-6 content,serum PCT content,and serum CRP content before treatment(P>0.05).After treatment,the daytime cough symptoms,serum IL-6,serum PCT and serum CRP in both groups significantly decreased compared to before treatment,and the above indicators in the AST+IM group were lower than those in the AST group(P<0.05).In terms of clinical characteristics,CCAMP-PHCLS children lost cough,fever and lung rales in the AST+IM group were shorter than the AST group(P<0.05),and the MP-IgM conversion rate was significantly higher than the AST group(P<0.05).In addition,in terms of clinical efficacy and safety,the total response rate of CCAMP-PHCLS in the AST+IM group was significantly higher than that in the AST group(P<0.05),while the incidence of adverse reactions of CCAMP-PHCLS in the AST+IM group was significantly lower than that in the AST group(P<0.05).Conclusion IM combined with AST has significant efficacy and high safety in children with CCAMP.The potential possible mechanism is that IM mediate production of inflammatory factors,and improves airway inflammation,thus alleviating clinical symptoms and signs.
3.Genetic study of a rare Chinese pedigree with a recombination occurring between the HLA-A/C loci in both parents
Tianju WANG ; Manni WANG ; Jun QI ; Yuhui LI ; Junhua WU ; Lixia SHANG ; Le CHEN
Chinese Journal of Medical Genetics 2024;41(7):853-857
Objective:To analyze a Chinese pedigree with a recombination occurring between the HLA- A/ C loci in both parents. Methods:A patient who was planning to undergo hematopoietic stem cell transplantation due to "aplastic anemia" in February 2022 was selected as the study subject. Peripheral blood samples were collected from the patient, his parents and brother. HLA- A/ C/ B/ DRB1/ DQB1 high-resolution typing was carried out by using sequence-based typing and sequence-specific oligonucleotides. The recombination was identified by pedigree analysis. The HLA haplotype of each individual was identified by genealogical analysis. The parentage possibility was determined by short tandem repeat analysis. HLA- A/ C/ B/ DRB1/ DRB345/ DQA1/ DQB1/ DPA1/ DPB1 were determined with next-generation high-throughput sequence-based typing. The recombination sites were analyzed by family study. Results:The high parentage possibilities of the family was confirmed by short tandem repeat analysis. Recombination was found between the HLA- A* 24: 02 A* 33: 03/ C* 14: 03 in the paternally transmitted haplotype, whilst HLA- A* 01: 01 A* 03: 01/ C* 08: 02 was found in the maternally transmitted haplotype, which had resulted in two novel HLA haplotypes in the proband. Conclusion:A rare case with simultaneous recombination of the paternal and maternal HLA- A/ C loci has been discovered, which may facilitate further study of the mechanisms of the HLA recombination.
4.Study on the extensibility of platelet donor gene database in Shaanxi
Jun QI ; Xiaoli CAO ; Xin HU ; Fengqin LI ; Zhendong SUN ; Yuhui LI ; Manni WANG ; Tianju WANG ; Junhua WU ; Lixia SHANG ; Le CHEN ; Hua XU
Chinese Journal of Blood Transfusion 2023;36(7):637-641
【Objective】 To analyze the commonality and characteristics between voluntary blood donors and hematopoietic stem cell donors in this region, and explore the potential for integration and development between China Marrow Donors Program (CMDP) and voluntary blood donors, especially platelet donor databases, so as to improve recruitment success rate and inventory rate. 【Methods】 The database modeling and comparison methods were used to screen and stratify the matching and integration degree between the voluntary blood donors in recent 10 years and the marrow donors in the Shaanxi Branch of CMDP. The frequencies of HLA-A,-B alleles, HPA alleles and haplotypes were calculated with Arlequin 3. 5. 2. 2 software, and the matching probability of different platelet donor reserve pools was conducted according to the phenotypic frequencies. 【Results】 Among the voluntary donors with known HLA genotypes in this region, according to their blood donation behavior,the active blood donors excavated were divided into the first, second, third and fourth echelons of platelet donor reserve pools, with 696, 2 752, 9 092 and 12 028 donors, respectively. The first echelon had the highest proportion of 10-50 times of platelet donations and 10-20 times of whole blood donations, with 13.65% and 26.01%, respectively. The second echelon had 10-20 times of whole blood donations and 10-50 times of platelet donations, accounted for 15.04% and 1.38%, respectively, which were significantly different from other echelons' blood donation characteristics (P<0.05). With a database size of the existing platelet donor bank adding the first and second echelons (n=4 955), there was a 69.02% probability of matching at least one donor with matching HLA-A-B phenotype. When considering the matching ABO and HPA phenotypes, the probability of finding at least one donor with fully matching HLA, HPA and ABO isotype (type B as an example) was 48. 73%. 【Conclusion】 The three groups of whole blood donation, apheresis platelet donation and marrow donation in Xi'an area have a large cross-distribution. Compared with expanding the storage capacity from scratch, the active blood donors in CMDP database are the largest back-up force of platelet donors. While expanding the effective storage capacity, it can minimize the cost of building platelet donor bank and the demand for resources.
5.The capacity evaluation and utilization strategy of the platelet donor database with known HLA/HPA genotype in Shaanxi
Jun QI ; Yuhui LI ; Tianju WANG ; Fengqin LI ; Junhua WU ; Lixia SHANG ; Le CHEN ; Manni WANG ; Jie FANG ; Hua XU
Chinese Journal of Blood Transfusion 2022;35(8):799-804
【Objective】 To evaluate the appropriate optimal capacity and matching probability of the platelet donor database with known HLA/HPA genotype in Shaanxi aera, and provide data support for subsequent construction, maintenance and application of the local platelet donor database. 【Methods】 A total of 11 755 individuals from the Shaanxi Branch of China Marrow Donor Program, 401 and 249 unrelated random platelet donors in Shaanxi aera were enrolled to the population study of HLA-A, -B polymorphisms, HPA genotyping and CD36 antigen expression, respectively. The frequencies of HLA-A, -B alleles, HPA alleles and haplotypes were calculated with Arlequin 3. 5. 2. 2 software; matching probability and capacity evaluation of platelet donor database was conducted according to the phenotypic frequencies. 【Results】 The population genetic and phenotypic polymorphisms data of HLA-A, -B and HPA1-6, 10, 15, 21 in Shaanxi aera were obtained. The frequency of CD36 type Ⅰ or Ⅱ deficiency was 0.40%(1/249). According to the subsequent calculating and deriving, with a database size of 194 donors, the patient having approximate 95% probability could achieve matching of HPA1-6, 10, 15, 21 genotype. With a database size of 1500 donors, there is a 95% probability of matching at least one donor with HLA-A-B phenotype frequency >0.002 or haplotype frequency >0.001; meanwhile, the probability of matching a cross-reactive group donor should be 44.95%-97.57%. Based on database size of 8 856 and 15 033, the probabilities of matching HLA-A, -B phenotype were about 80% and 90%, respectively. 【Conclusion】 The differences in the distribution of HLA/HPA polymorphism in different regions make the establishment mode and optimal capacity of platelet donor database different. It is necessary to apply a variety of platelet matching transfusion strategies to expand the range of donor selection, thereby effectively reducing the database construction cost and resource requirements.
6.Characterization of a rare HLA-C*08:84 allele and analysis of its 3-D molecular structure.
Tianju WANG ; Jun QI ; Hengxin LI ; Jian HAO ; Xiaofang WANG ; Manni WANG ; Jie FANG ; Junhua WU ; Lixia SHANG ; Le CHEN
Chinese Journal of Medical Genetics 2021;38(8):798-802
OBJECTIVE:
To verify a rare allele of human leukocyte antigen (HLA) and analyze its inheritance and 3D molecular structure.
METHODS:
PCR-sequence-based typing, PCR-single strand oligonucleotide polymorphism and single allele-specific sequencing were carried out to characterize the rare HLA-C allele and its transmission in the family. Its protein structure was modeled by using SWISS-MODEL, Phyre2 and FATCAT software.
RESULTS:
Analysis indicated that the rare allele (HLA-C*08:84) has transmitted from the proband's mother and has differed from HLA-C*08:01 by a single base (g.512G>C), resulting in substitution of an amino acid (p.Trp147Ser). Modeling of the 3D structure of the encoded protein indicated that the amino acid residue variation is located at the alpha 2 helix, which participates the formation of pocket F. Modeling of the structures of C*08:84, C*08:01, C*08:02, C*08:03 and C*08:22 has suggested significant variation in the peptide binding regions of the backbone, with root mean square errors being 1.70 nm, 1.79 nm, 0.71 nm and 1.70 nm, respectively.
CONCLUSION
A rare HLA-C*08:84 allele has been identified, and its clinical significance has been analyzed.
Alleles
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Base Sequence
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HLA-B Antigens/genetics*
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HLA-C Antigens/genetics*
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Humans
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Molecular Structure
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Sequence Analysis, DNA
7.DNA-PK inhibition by M3814 enhances chemosensitivity in non-small cell lung cancer.
Manni WANG ; Siyuan CHEN ; Yuquan WEI ; Xiawei WEI
Acta Pharmaceutica Sinica B 2021;11(12):3935-3949
A significant proportion of non-small cell lung cancer (NSCLC) patients experience accumulating chemotherapy-related adverse events, motivating the design of chemosensitizating strategies. The main cytotoxic damage induced by chemotherapeutic agents is DNA double-strand breaks (DSB). It is thus conceivable that DNA-dependent protein kinase (DNA-PK) inhibitors which attenuate DNA repair would enhance the anti-tumor effect of chemotherapy. The present study aims to systematically evaluate the efficacy and safety of a novel DNA-PK inhibitor M3814 in synergy with chemotherapies on NSCLC. We identified increased expression of DNA-PK in human NSCLC tissues which was associated with poor prognosis. M3814 potentiated the anti-tumor effect of paclitaxel and etoposide in A549, H460 and H1703 NSCLC cell lines. In the four combinations based on two NSCLC xenograft models and two chemotherapy, we also observed tumor regression at tolerated doses
8.Association of HLA-DRB1, -DQB1, -DPB1 alleles and haplotype polymorphisms with acute myeloid leukemia (non-M3 ) in northern Han population
Jun QI ; Tianju WANG ; Le CHEN ; Manni WANG ; Xiaofang WANG ; Dan DU ; Lixia SHANG ; Junhua WU ; Jie FANG ; Hengxin LI
Chinese Journal of Blood Transfusion 2021;34(2):101-106
【Objective】 To explore the association of HLAII(-DRB1, -DQB1, -DPB1) alleles and haplotypes polymorphisms with acute myeloid leukemia (AML) in northern Han population. 【Methods】 A total of 308 AML (non-M
9. Effect of radiotherapy on ovarian function in patients undergoing radical surgery for cervical cancer
Jusheng AN ; Xiaomeng DU ; Feng ZHANG ; Jiayun CHEN ; Jianrong DAI ; Manni HUANG ; Lingying WU
Chinese Journal of Radiation Oncology 2019;28(10):753-757
Objective:
The correlation between dosimetric parameters of transposed ovary and different clinical ovarian functional status was assessed in young patients with cervical cancer who needed adjuvant radiotherapy after radical resection of the ⅠB1-ⅡA2 phase of preserved and transposed ovaries.
Methods:
The function of transposed ovary and relevant clinical symptoms in 86 patients before and 2 years after treatment between 2015 and 2017 were retrospectively analyzed, and the correlation between the dosimetric parameters and functional status of transposed ovaries during radiotherapy was evaluated. Different
10.Analysis of Risk Factors for Cesarean Section after Induction of Late-term Pregnancy
Manni SUN ; Haiying CHEN ; Tao MENG
Journal of China Medical University 2018;47(2):111-113,118
Objective To explore the risk factors for cesarean section after induction of late-term pregnancy. Methods This study enrolled 275 primiparas with a single cephalic fetal presentation,admitted to our hospital between December 2010 and December 2016 for induction of late-term pregnancy. After induction,80 underwent cesarean section and 195 had a normal vaginal delivery. Clinical data were collected and analyzed retrospectively. Single factor analysis and two categories of logistic regression analysis were used to determine the independent risk factors for cesarean section after induction of late-term pregnancy. Results Single factor analysis showed that the differences between the two groups in maternal height,cervical Bishop score before induction of labor,latent phase,intrapartum amniotomy,intrapartum oxytocin,meconium stained amniotic fluid,and birth weight were statistically significant (P < 0. 05). Multivariate analysis showed that maternal height,cervical Bishop score before induction of labor,and latent phase were independent risk factors for cesarean section after induction of late-term pregnancy. Conclusion Late-term pregnant primiparas with short stature,low Bishop score,or a long latent phase should have comprehensive prenatal maternal-fetal assessment,and a reasonable delivery mode should be chosen to avoid adverse outcomes.

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