1.Serological and molecular biological analysis of a rare Dc- variant individual
Xue TIAN ; Hua XU ; Sha YANG ; Suili LUO ; Qinqin ZUO ; Liangzi ZHANG ; Xiaoyue CHU ; Jin WANG ; Dazhou WU ; Na FENG
Chinese Journal of Blood Transfusion 2025;38(8):1101-1106
Objective: To reveal the molecular biological mechanism of a rare Dc-variant individual using PacBio third-generation sequencing technology. Methods: ABO and Rh blood type identification, DAT, unexpected antibody screening and D antigen enhancement test were conducted by serological testing. The absorption-elution test was used to detect the e antigen. RHCE gene typing was performed by PCR-SSP, and the 1-10 exons of RHCE were sequenced by Sanger sequencing. The full-length sequences of RHCE, RHD and RHAG were detected by PacBio third-generation sequencing technology. Results: Serological findings: Blood type O, Dc-phenotype, DAT negative, unexpected antibody screening negative; enhanced D antigen expression; no detection of e antigen in the absorption-elution test. PCR-SSP genotyping indicated the presence of only the RHCE
c allele. Sanger sequencing results: Exons 5-9 of RHCE were deleted, exon 1 had a heterozygous mutation at c. 48G/C, and exon 2 had five heterozygous mutations at c. 150C/T, c. 178C/A, c. 201A/G, c. 203A/G and c. 307C/T. Third-generation sequencing results: RHCE genotype was RHCE
02N. 08/RHCE-D(5-9)-CE; RHD genotype was RHD
01/RHD
01; RHAG genotype was RHAG
01/RHAG
01 (c. 808G>A and c. 861G>A). Conclusion: This Dc-individual carries the allele RHCE
02N. 08 and the novel allele RHCE-D(5-9)-CE. The findings of this study provide data support and a theoretical basis for elucidating the molecular mechanisms underlying RhCE deficiency phenotypes.
2.Discovery and mechanism verification of first-in-class hydrophobic tagging-based degraders of HBV core protein.
Shujing XU ; Ya WANG ; Dazhou SHI ; Shuo WANG ; Lijun QIAO ; Ge YANG ; Yang ZHOU ; Xinyong LIU ; Shuo WU ; Yuhuan LI ; Peng ZHAN
Acta Pharmaceutica Sinica B 2025;15(4):2170-2196
Interfering hepatitis B virus (HBV) capsid assembly holds promise as a therapeutic approach for chronic hepatitis B (CHB). Novel anti-HBV agents are urgently needed to overcome drug resistance challenges, with targeted protein degradation (TPD) emerging as a hopeful strategy. Herein, we report the first degradation of HBV core protein (HBC), a multifunctional structural protein, using small-molecule degraders developed by hydrophobic tagging (HyT) technology. Structure-activity relationship (SAR) analysis identified compound HyT-S7, featuring an adamantyl group, exhibiting potent inhibitory activity (EC50 = 0.46 μmol/L, HepAD38 cells) and degradation ability (DC50 = 3.02 ± 0.54 μmol/L) in a dose- and time-dependent manner. Mechanistic studies demonstrated that the autophagy-lysosome pathway was a potential driver of HyT-S7-induced HBC degradation. Remarkably, HyT-S7 effectively degraded 11 drug-resistant mutants, including highly resistant strains P25G and T33N, to Phase III drug GLS4. Furthermore, cellular thermal shift assay, surface plasmon resonance assay, and molecular dynamics simulations revealed the precise mode of HyT-S7 binding to HBC with the adamantyl group potentially mimicking protein misfolding to facilitate HBC degradation. This first proof-of-concept study highlights the potential of HyT-mediated TPD in HBC as a promising avenue for discovering novel HBV and other antiviral agents with favorable drug resistance profiles.
3.Differentiating lymphoma from lymphoid inflammatory hyperplasia using 18 F-FDG PET/CT radiomics combined with clinical features
Liang Xie ; Jialin Qin ; Ruixue Wu ; Chunfeng Xiang ; Pengfei Fang ; Chenfeng Shou ; Hong Chen ; Xiaoxi Pang
Acta Universitatis Medicinalis Anhui 2025;60(5):954-963
Objective :
To develop and to validate a combined model integrating18F-FDG PET/CT radiomics with clinical features to distinguish between lymphoma and lymphoid inflammatory hyperplasia.
Methods :
A retrospective study was conducted on a cohort of 232 patients diagnosed with lymphoma or lymphoid inflammatory hyperplasia. Comparative analyses of clinical and traditional imaging indicators were performed to identify inter-group differences. The clinical features were delineated and extracted using medical software including 3D-Slicer and Lifex. Selection of the features was performed to construct a PET/CT-based radiomics Logistic model, with a combined model integrating PET/CT with clinical features then used to evaluate the discriminative efficacy of these models.
Results:
Analysis of inter-group differences indicated that age, CTmean, and metabolic tumor volume(MTV)were effective for differentiating between lymphoma and lymphoid inflammatory hyperplasia(P<0.05). The PET/CT-based radiomics Logistic model differentiated between lymphoma and lymphoid inflammatory hyperplasia, with an area under curve(AUC) of 0.924(95%CI: 0.884-0.960) and 0.863(95%CI: 0.774-0.939) in the training and testing cohorts, respectively. The integrated Logistic model that combined PET/CT-based radiomics with clinical features to distinguish between lymphoma and lymphoid inflammatory hyperplasia achieved an AUC of 0.933(95%CI: 0.889-0.969) in the training cohort and 0.884(95%CI: 0.792-0.964) in the testing cohort. Decision curve analysis(DCA) demonstrated that the integrated model provided the greatest clinical net benefit.
Conclusion
The hybrid model integrating18F-FDG PET/CT radiomics with clinical features shows robust diagnostic efficacy to distinguish between lymphoma and lymphoid inflammatory hyperplasia.
4.Immunogenicity of red blood cell blood group antigens in the population of Xi'an
Liangzi ZHANG ; Qinqin ZUO ; Hua XU ; Yong ZHANG ; Dazhou WU ; Xue TIAN ; Xiaoyue CHU
Chinese Journal of Blood Transfusion 2024;37(12):1394-1398
[Abstract] [Objective] To evaluate the immunogenicity of red blood cell blood group antigens in the population of Xi'an. [Methods] Data on blood group antigens of voluntary blood donors from the Shaanxi Province Blood Center and unexpected antibody detection results from clinically submitted cases between January 2019 and May 2024 were analyzed. The Giblett blood group antigen immunogenicity calculation formula was used to calculate the immunogenicity of blood group antigens based on the frequency of unexpected antibodies and the probability of antigen-negative patients receiving antigen-positive red blood cells. The relative immunogenicity of each blood group antigen was obtained by multiplying the immunogenicity of the K antigen (0.095). [Results] A total of 30 921 individuals were included for red blood cell blood group antigen analysis, with 511 cases of unexpected antibody identification. The ranking of red blood cell blood group antigen immunogenicity for the overall population was: Wra>E>Dib>Fya>K>C>e>c>Dia>Jka>M>Lea>Jkb>Leb>Fyb>S, while for males, it was: Dib>Wra>E>K>Fya>C>e>c>M>Dia>Jka>Fyb>Lea>Leb>Jkb>S. [Conclusion] Based on the immunogenicity ranking from strong to weak of red blood cell antigens in the population of Xi'an, this study provides theoretical support for the expansion and matching of antigens, and technical support for achieving precise red blood cell transfusions to improve transfusion efficacy and safety.
5.Baseline survey of psychosocial factors levels and their health effects in a cohort study of natural gas field workers.
Hui WU ; Jian Zhong SHAO ; Gui Zhen GU ; Fu Ran LI ; Wen Hui ZHOU ; Shan Fa YU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(3):183-188
Objective: To investigate the level of psychosocial factors in workplace and their health effects among workers in a natural gas field. Methods: A prospective and open cohort of natural gas field workers was established to study the level of workplace psychosocial factors and their health effects, with a follow-up every 5 years. In October 2018, a cluster sampling method was used to conduct a baseline survey of 1737 workers in a natural gas field, including a questionnaire survey on demographic characteristics, workplace psychosocial factors and mental health outcomes, physiological indicators such as height and weight, and biochemical indicators such as blood routine, urine routine, liver function and kidney function. The baseline data of the workers were statistically described and analyzed. The psychosocial factors and mental health outcomes were divided into high and low groups according to the mean score, and the physiological and biochemical indicators were divided into normal and abnormal groups according to the reference range of normal values. Results: The age of 1737 natural gas field workers was (41.8±8.0) years old, and the length of service was (21.0±9.7) years. There were 1470 male workers (84.6%). There were 773 (44.5%) high school (technical secondary school) and 827 (47.6%) college (junior college) graduates, 1490 (85.8%) married (including remarriage after divorce), 641 (36.9%) smokers and 835 (48.1%) drinkers. Among the psychosocial factors, the detection rates of high levels of resilience, self-efficacy, colleague support and positive emotion were all higher than 50%. Among the mental health outcomes evaluation indexes, the detection rates of high levels of sleep disorder, job satisfaction and daily stress were 41.82% (716/1712), 57.25% (960/1677) and 45.87% (794/1731), respectively. The detection rate of depressive symptoms was 22.77% (383/1682). The abnormal rates of body mass index (BMI), triglyceride and low density lipoprotein were 46.74% (810/1733), 36.50% (634/1737) and 27.98% (486/1737), respectively. The abnormal rates of systolic blood pressure, diastolic blood pressure, uric acid, total cholesterol and blood glucose were 21.64% (375/1733), 21.41% (371/1733), 20.67% (359/1737), 20.55% (357/1737) and 19.17% (333/1737), respectively. The prevalence rates of hypertension and diabetes were 11.23% (195/1737) and 3.45% (60/1737), respectively. Conclusion: The detection rates of high level psychosocial factors in natural gas field workers are high, and their effects on physical and mental health remain to be verified. The establishment of a cohort study of the levels and health effects of psychosocial factors provides an important resource for confirming the causal relationship between workplace psychosocial factors and health.
Humans
;
Male
;
Adult
;
Middle Aged
;
Natural Gas
;
Cohort Studies
;
Prospective Studies
;
Oil and Gas Fields
;
Workplace/psychology*
;
Surveys and Questionnaires
6.Application and evaluation of human antibodies in ABO grouping
Qinqin ZUO ; Liangzi ZHANG ; Dazhou WU ; Yong ZHANG ; Xiaoyue CHU ; Weiwei ZHANG ; Hong WANG ; Juan MAO ; Hua XU
Chinese Journal of Blood Transfusion 2023;36(10):928-931
【Objective】 To evaluate the application of monoclonal typing reagents and human anti-A/B antibodies for absorption-elution test in ABO grouping. 【Methods】 The specificity of monoclonal typing reagents and human anti-A/B antibodies with standard A, B, O and AB phenotypes at 4 ℃, room temperature, and 37 ℃ were compared. Affinity was evaluated by the titer, agglutination time and agglutination intensity of the reaction with A1/B cells. 29 samples with ABO discrepancy were tested to evaluate the ability of monoclonal typing reagents and human anti-A/B antibodies to detect weak antigens in absorption-elution test. 【Results】 The specificity and affinity of human anti-A/B antibodies are low, and monoclonal typing reagents have cross reactivity. Human anti-A/B antibodies can detect most weak antigens in absorption-elution test with no cross reactivity. 【Conclusion】 In ABO grouping, the human anti A/B antibody binding absorption-elution test can serve as a supplement method for identifying ABO weak antigens. Accurate results can be obtained with reasonable reagents and corresponding methodology in serological tests,thus ensuring the safety of blood transfusion.
7.Establishment of Shaanxi rare blood group information supply platform
Liangzi ZHANG ; Qinqin ZUO ; Dazhou WU ; Yong ZHANG ; Xiaoyue CHU ; Weiwei ZHANG ; Hong WANG ; Juan MAO ; Hua XU
Chinese Journal of Blood Transfusion 2023;36(10):949-952
【Objective】 To establish a rare blood group information supply platform in Shaanxi Province. 【Methods】 The rare blood group information supply platform consists of sample registration, result registration, donor files and inventory blood. The blood donation codes of voluntary blood donors were recorded for blood typing, and the antigen identification results of each blood group system were registered, all stored in the rare blood type information supply platform. When receiving an application for unusual or rare blood type missing multiple conventional antigens or a certain high-frequency antigen, the corresponding antigen negative blood donors and their blood status (in stock or not) were queried from the donor profile module of the platform, and the inventory of blood of rare blood type was monitored dynamically. 【Results】 The results showed that 5.060% (273/5 398) of rare Rh phenotype donors, 1.540‰ (51/33 010) of donors lacking multiple regular antigens, and 13 O-type donors lacking high-frequency antigens were recorded in the rare blood type information supply platform. Among them, 0.019‰ (3/158 484) of Jk(a-b-) phenotype, 0.436‰ (2/4 586) of Di(a+b-) phenotype, and 4.030‰ (8/1 983) of Fy (a-b+) phenotype were stored in the blood bank for rare blood type. 【Conclusion】 The establishment of rare blood group information supply platform can meet the urgent demand for blood of rare blood types in clinical practice and ensure the safety of blood transfusion.
8.Hemolytic disease of newborn caused by unexpected antibodies: a retrospective study of 287 cases
Liangzi ZHANG ; Qinqin ZUO ; Dazhou WU ; Yong ZHANG ; Hong WANG ; Xiaoyue CHU ; Juan MAO ; Weiwei ZHANG ; Hua XU
Chinese Journal of Blood Transfusion 2023;36(1):42-44
【Objective】 To observe the distribution of non-ABO-HDN and its clinical relevance, so as to provide reference for clinical diagnosis and treatment. 【Methods】 A total of 287 cases of non-ABO-HDN recorded during January 2012 to August 2022 were enrolled and tested in our laboratory. The correlation between maternal history of blood transfusion, pregnancy, unexpected antibody titers, gender, ABO-HDN and transfusion therapy was analyzed by chi-square test. 【Results】 All 287 cases of non-ABO-HDN involved 13 kinds of unexpected antibodies of 6 blood group systems. Rh-HDN accounted for 96.17% (276/287), and anti-D-HDN accounted for 47.04% (135/287). The proportion of non-ABO-HDN patients without ABO-HDN requiring exchange/transfusion was significantly higher than that of non-ABO-HDN patients with ABO-HDN(P<0.05). The ratio of need for exchange/transfusion in the high titer group (>8) was significantly higher than that in the low titer group (≤8) (P<0.05). There was no significant difference in gender, mother′s history of blood transfusion, pregnancy and whether or not to exchange/transfusion (severity of illness). 【Conclusion】 Understanding the characteristics of non-ABO-HDN and the specific distribution of unexpected antibodies, the correlation between various factors and diseases and their clinical significance are conductive to timely taking necessary intervention measures and reducing the risk of complications.
9.Establishment and clinical application of Kidd, Diego, Duffy blood group system, Shaanxi Province
Xiaoyue CHU ; Yong ZHANG ; Juan MAO ; Liangzi ZHANG ; Qinqin ZUO ; Weiwei ZHANG ; Dazhou WU ; Hong WANG ; Hua XU
Chinese Journal of Blood Transfusion 2022;35(11):1124-1127
【Objective】 To screen individuals with rare blood type of Kidd, Diego, Duffy blood group system among the voluntary blood donor in Shaanxi province and to establish on-line and physical database of rare blood type. 【Methods】 Jk(a-b-)phenotype donors were screened by 2 mol/L urea hemolysis test. Blood donors with Di(a+ b-) phenotype were screened by genotyping; Fy(a-) and D-- phenotype donors were screened by modified antiglobulin assay. 【Results】 Three cases of Jk(a-b-) phenotype were detected out of 158 484 voluntary blood donors. The distribution frequency of Jk(a-b-) phenotype was 0.019‰. Di(a+ b-) phenotype was detected in 2(0.436‰) cases out of 4 586 voluntary blood donor. Fy(a-) phenotype was detected in 8(4.034‰) cases out of 1 983 voluntary blood donors. D-- phenotype was not detected in 29 430 voluntary blood donors. 【Conclusion】 The on-line database of Kidd, Diego, Duffy blood group system had been established by large-size screening of blood donor samples, which can conclude the region′s population distribution and genetic characteristics of RBC blood group. And physical database could further be established using the technology of red blood cells cryopreservation when the conditionspermit, so as to provide the most compatible blood for the clinical effectively improve blood transfusion safety, and provide data support for blood early warning.


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