1.Structural and Spatial Analysis of The Recognition Relationship Between Influenza A Virus Neuraminidase Antigenic Epitopes and Antibodies
Zheng ZHU ; Zheng-Shan CHEN ; Guan-Ying ZHANG ; Ting FANG ; Pu FAN ; Lei BI ; Yue CUI ; Ze-Ya LI ; Chun-Yi SU ; Xiang-Yang CHI ; Chang-Ming YU
Progress in Biochemistry and Biophysics 2025;52(4):957-969
ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.
2.The mediating effect of perceived social support in the relationship between maternal personality traits and pregnancy-related anxiety.
Jia Shu ZHU ; Rui WANG ; Ye LI ; You Juan FU ; Hong Ya LIU ; Jia Qi LI ; Gui Xiang YAO ; Su Zhen GUAN
Chinese Journal of Preventive Medicine 2023;57(2):187-192
Objective: Exploring the mediating effect of perceived social support between the maternal personality traits and pregnancy-related anxiety. Methods: Singleton pregnant women who underwent antenatal checkups in the obstetrics department of general hospital affiliated to Ningxia Medical University from July to December 2021 were enrolled in this study to investigate perceived social support, pregnancy-related anxiety and conscious personality traits. Pearson correlation analysis was used to analyze the association between the maternal personality traits, perceived social support, and pregnancy-related anxiety, and the mediating effect of perceived social support was analyzed using Bootstrap method. Results: A total of 1 259 subjects were included in the study, of which 170 (13.50%) pregnant women felt introverted. The total score of perceived social support was (46.37±8.38), and 31.45% of pregnant women had high perceived social support. The total score of pregnancy-related anxiety was (21.48±5.53). The score of worry about fetal health was (10.09±3.24), and 368 (29.23%) of pregnant women had pregnancy-related anxiety. Maternal personality traits and pregnancy-related anxiety were negatively correlated (r=-0.076, P<0.05) and positively correlated with perceived social support during pregnancy (r= 0.127, P<0.05). Perceived social support during pregnancy and pregnancy-related anxiety were negatively correlated (r=-0.236, P<0.05). Perceived social support partially mediated the relationship between the maternal personality traits and pregnancy-related anxiety, with a relative effect value of 37.50%. Conclusion: The maternal personality traits, level of perceived social support and pregnancy-related anxiety are all related. Perceived social support could mediate the relationship between the maternal personality traits and pregnancy-related anxiety.
Female
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Pregnancy
;
Humans
;
Anxiety
;
Pregnant Women
;
Personality
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Social Support
;
Prenatal Care
3.Modern research progress in external application of traditional Chinese medicine to acupoints.
Wei-Feng ZHU ; Ya-Qi WANG ; Wen-Ting WU ; Zhe LI ; Li-Li LIU ; Zhi-Yu GUAN ; Li-Hua CHEN ; Yong-Mei GUAN
China Journal of Chinese Materia Medica 2023;48(3):579-587
Traditional Chinese medicine(TCM) has a long history and abundant experience in external therapy, which marks human wisdom. In the early history of human, people found that fumigation, coating, and sticking of some tree branches and herb stems can help alleviate scabies and remove parasites in productive labor, which indicates the emergence of external therapy. Pathogen usually enters the body through the surface, so external therapy can be used to treat the disease. External therapy is among the major characteristic of surgery of TCM. As one of the external therapies in TCM, external application to acupoints smooths the zang-fu organs through meridians and collaterals, thereby harmonizing yin and yang. This therapy emerged in the early society, formed the Spring and Autumn Period and the Warring States Period, improved in the Song and Ming dynasties, and matured in the Qing dynasty. With the efforts of experts in history, it has had a mature theory. According to modern research, it can avoid the first-pass effect of liver and the gastrointestinal irritation and improve the bioavailability of Chinese medicine. Based on the effect of Chinese medicine and the theory of meridian and collateral, it can stimulate the acupoints, exert regulatory effect on acupoints, and give full play to the efficacy of TCM and the interaction of the two. Thereby, it can regulate qi and blood and balance yin and yang, thus being widely used in the treatment of diseases. In this paper, the use of external application to acupoints, the effect on skin immunity, the regulation of neuro-inflammatory mechanism, the relationship between acupoint application and human circulation network, and the development of its dosage form were summarized through literature review. On this basis, this study is expected to lay a foundation for further research.
Humans
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Acupuncture Points
;
Biological Availability
;
Fumigation
;
Medicine, Chinese Traditional
;
Meridians
4.Design of remote diabetes management system based on dynamic blood glucose monitoring
Wei DAI ; Yang GUAN ; Yun LI ; Xin-Peng WANG ; Ya ZHU ; Hui-Zi LI
Chinese Medical Equipment Journal 2023;44(9):42-48
Objective To design a remote diabetes management system based on dynamic blood glucose monitoring to solve the problems of traditional diabetes patient management in glucose data manual collection,unidirectional information flow and out-hospital glucose management.Methods A remote diabetes management system was developed with Java EE distributed microservices-based architecture and front-end and back-end separation mode,which used Vue for the front-end user interface design and IntelliJ IDEA development tools supporting Java language for the backend.The system developed was composed of a doctor App,a patient App and a background management terminal.The doctor App had three modules for user management,data viewing and intervention follow-up,the patient App had three modules for data monitoring,event recording and doctor-patient communication and the background management terminal had three modules for user management,data management and device management.Results The system developed realized individualized intervention and long-term glucose control based on real-time data acquisition of patient glucose fluctuation,diet,medication,exercise and other conditions.Conclusion The system developed can be used for the centralized online and offline management for in-hospital and out-hospital diabetes patients,which reduces the incidence of adverse events due to high or low blood glucose and improves the efficiency of medical staffs.[Chinese Medical Equipment Journal,2023,44(9):42-48]
5.Consensus of experts on the medical risk prevention for the patients with cardiovascular diseases during dental treatment (2022 edition).
Jing ZHANG ; Guan Hua SU ; Xiao Dong ZHANG ; Kai XU ; Zuo Min WANG ; Xu Liang DENG ; Ya Qin ZHU ; Yong Jin CHEN ; Cheng Zhi GAO ; Hong XIE ; Xuan PAN ; Lin YIN ; Bao Hua XU ; Wei FEI ; Jian ZHOU ; Dan SHAO ; Zhi Hong ZHANG ; Kai ZHANG ; Xia WANG ; Xiang CHENG ; Xiao WANG ; Li Li CHEN
Chinese Journal of Stomatology 2022;57(5):462-473
With the aging process of population in the society, the prevalence of cardiovascular diseases (CVD) in China is increasing continuously and the number of dental patients with CVD is increasing gradually too. Due to the lack of guidelines for dental patients with CVD in our country, how to implement standardized preoperative evaluation and perioperative risk prevention remains a problem to be solved for dentists at present. The present expert consensus was reached by combining the clinical experiences of the expert group of the Fifth General Dentistry Special Committee, Chinese Stomatological Association and respiratory and cardiology experts in diagnosis and treatment for CVD patients, and by systematically summarizing the relevant international guidelines and literature regarding the relationship between CVD and oral diseases and the diagnosis and treatment of dental patients with heart failure, hypertension and antithrombotic therapy. The consensus aims to provide, for the dental clinicians, the criteria on diagnosis and treatment of CVD in dental patients in China so as to reduce the risk and complications, and finally to improve the treatment levels of dental patients with CVD in China.
Cardiovascular Diseases/prevention & control*
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China/epidemiology*
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Consensus
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Dental Care
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Humans
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Oral Medicine
6.Study on emergency metabolic changes of Anopheles sinensis larvae following exposure to deltamethrin
Ya-Shu LI ; Jian-Xia TANG ; Ju-Lin LI ; Cheng LIANG ; Mei-Hua ZHANG ; Jing-Yao WU ; Guan-Xi WANG ; Guo-Ding ZHU ; Jun CAO
Chinese Journal of Schistosomiasis Control 2021;33(4):387-395
Objective To analyze the changes of small molecular metabolites in the larvae of a deltamethrin-sensitive strain of Anopheles sinensis following exposure to deltamethrin, so as to provide the scientific basis for investigating the metabolic pathway and screening metabolic markers of deltamethrin in An. sinensis. Methods The 50% and 75% lethal concentrations (LC50 and LC75) of deltamethrin against the larvae of a deltamethrin-sensitive strain of An. sinensis were calculated in laboratory. The type and content of An. sinensis larvae metabolites were detected using high performance liquid chromatography and mass spectrometry (LC-MS/MS) following exposure to deltamethrin at LC50 and LC75 for 30 min and 24 h, and the changes of metabolites were analyzed. Results The LC50 and LC75 values of deltamethrin were 4.36 × 10-3 µg/mL and 1.12 × 10-2 µg/mL against thelarvae of a deltamethrin-sensitive strain of An. sinensis. Following exposure of the larvae of a deltamethrin-sensitive strain of An. sinensis to deltamethrin at LC50 and LC75 for 30 min, the differential metabolites mainly included organic oxygen compounds, carboxylic acid and its derivatives, fatty acyl and pyrimidine nucleotides, with reduced glucose levels. Following exposure for 24 h, the differential metabolites mainly included organic oxygen compounds, carboxylic acid and its derivatives, aliphatic acyl and purine nucleotides, with increased glucose level detected. Conclusion Carbohydrate, carboxylic acid and its derivatives, fatty acyls, amino acids and their derivatives may play important roles in deltamethrin metabolism in the larvae of a deltamethrin-sensitive strain of An. sinensis.
7.Immunogenicity and safety of a recombinant fusion protein vaccine (V-01) against coronavirus disease 2019 in healthy adults: a randomized, double-blind, placebo-controlled, phase II trial.
Ya-Jun SHU ; Jian-Feng HE ; Rong-Juan PEI ; Peng HE ; Zhu-Hang HUANG ; Shao-Min CHEN ; Zhi-Qiang OU ; Jing-Long DENG ; Pei-Yu ZENG ; Jian ZHOU ; Yuan-Qin MIN ; Fei DENG ; Hua PENG ; Zheng ZHANG ; Bo WANG ; Zhong-Hui XU ; Wu-Xiang GUAN ; Zhong-Yu HU ; Ji-Kai ZHANG
Chinese Medical Journal 2021;134(16):1967-1976
BACKGROUND:
Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study.
METHODS:
A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization.
RESULTS:
V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively.
CONCLUSIONS:
The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy.
TRIAL REGISTRATION
http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
Aged
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Antibodies, Viral
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COVID-19/therapy*
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COVID-19 Vaccines
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Double-Blind Method
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Humans
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Immunization, Passive
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Recombinant Fusion Proteins
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SARS-CoV-2
8.Surveillance of Culex mosquitoes in Jiangsu Province from 2018 to 2019
Ju-Lin LI ; Jian-Xia TANG ; Jing-Yao WU ; Meng-Meng YANG ; Cheng LIANG ; Mei-Hua ZHANG ; Ya-Shu LI ; Guan-Xi WANG ; Hua-Yun ZHOU ; Guo-Ding ZHU ; Jun CAO
Chinese Journal of Schistosomiasis Control 2021;33(5):510-512
Objective To investigate the distribution and density of Culex mosquito populations and the resistance of Culex pipiens pallens to insecticides in Jiangsu Province in 2018 and 2019. Methods During the period from June to October in 2018 and 2019, six counties (districts, cities) were sampled in southern, northern and central Jiangsu Province as surveillance sites. The density of Culex mosquitoes was measured overnight using the light trapping technique. In addition, Culex pipiens pallens mosquitoes were collected from Hai’an of Nantong City and Yandu District of Yancheng City, central Jiangsu Province, and the sensitivity of female first filial generations to dichlorodiphenyltrichloroethane (DDT), malation, proposur, beta cypermethrin and deltamethrin was tested using the standard WHO insecticide susceptibility test assay. Results A total of 104 423 Culex mosquitoes were captured in six surveillance sites of Jiangsu Province in 2018 and 2019, and Culex quinquefasciatus (49.11%), Culex pipiens pallens (28.38%), and Culex tritaeniorhynchus (21.04%) were predominant species. The density of Culex mosquitoes started to increase since early June, peaked in July and tended to be low in late October. Culex pipiens pallens mosquitoes captured from Hai’an was susceptible to malation, while those from Yandu District were moderately resistant to malation. Culex pipiens pallens mosquitoes from both Yandu and Hai’an were moderately resistant to proposur, and were resistant to DDT, beta cypermethrin and deltamethrin. Conclusions Culex quinquefasciatus, Culex pipiens pallens and Culex tritaeniorhynchus are predominant Culex species in Jiangsu Province. Culex pipiens pallens is resistant to DT, beta cypermethrin and deltamethrin in central Jiangsu Province.
9.Establishment of skin and joint micro-dialysis sampling method of triptolide in vivo by HPLC-MS/MS.
Yong-Mei GUAN ; Jia LIU ; Ya-Ting YU ; Wei-Feng ZHU ; Li-Hua CHEN ; Chen JIN ; Zhen-Zhong ZANG
China Journal of Chinese Materia Medica 2019;44(16):3576-3581
To detect the concentration of triptolide in skin and joint after percutaneous administration,an HPLC-MS/MS method and skin and joint micro-dialysis( MD) method of triptolide were established in this study. The separation was achieved on triple quadrupole( AB QTRAP4500) and phenomenex-C18( 4. 6 mm×150 mm,5 μm,luna) column with acetonitrile-water with 0. 1% formic acid( 65 ∶35) as the mobile phase at a flow rate of 0. 7 m L·min-1. An electrospray ionization( ESI) source was applied and operated in the positive multiple reaction monitoring( MRM) mode. The fragment ion for triptolide was m/z 361. 1→145. 0. The effects of different perfusion [Ringer's,PBS( p H 7. 4),30% ethanol saline]drug concentrations and flow rates on the recovery rate,as well as the relationship between the recovery rate and the loss rate were determined by incremental( dialysis) and reduction( retrodialysis) methods.The reduction method was applied in the in vivo study to investigate and determine the stability of the probe recovery rate in 10 h. The results of HPLC-MS/MS detection method conformed to the requirements of biological samples. The perfusion fluid was 30% ethanol saline. The recovery rate of skin and joint probes in vitro of triptolide increased within the flow rate of 0. 5-2. 5 μL·min-1. In order to increase the timeliness of data and the accuracy,the flow rate was determined to be 1 μL·min-1,and the sample interval was determined to be 0. 5 h. The recovery rate of triptolide in skin and joint probes in vitro and the loss rate were stable and equal despite of change of triptolide concentration within 10-200 μg·L-1. This indicated that the effect of drug concentration on the MD probe recovery rate was small,and the recovery rate could be replaced by the loss rate. The loss rate in vivo using MD method was measured at 10 h,indicating that the transfer rate of triptolide was stable within 10 h. The established method of triptolide in MD and HPLC-MS/MS can be applied to investigate the kinetic in skin and joint after percutaneous administration of triptolide.
Chromatography, High Pressure Liquid
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Diterpenes
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pharmacokinetics
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Epoxy Compounds
;
pharmacokinetics
;
Humans
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Joints
;
metabolism
;
Phenanthrenes
;
pharmacokinetics
;
Reproducibility of Results
;
Skin
;
metabolism
;
Tandem Mass Spectrometry
10.An interlaboratory comparison study on the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels.
Ya Zhen QIN ; Li Wen ZHU ; Shang LIN ; Su Xia GENG ; Sheng Wei LIU ; Hui CHENG ; Cheng Ye WU ; Min XIAO ; Xiao Qing LI ; Rui Ping HU ; Li Li WANG ; Hai Yan LIU ; Dao Xin MA ; Tao GUAN ; Yuan Xin YE ; Ting NIU ; Jian Nong CEN ; Li Sha LU ; Li SUN ; Tong Hua YANG ; Yun Gui WANG ; Tao LI ; Yue WANG ; Qing Hua LI ; Xiao Su ZHAO ; Ling Di LI ; Wen Min CHEN ; Ling Yu LONG ; Xiao Jun HUANG
Chinese Journal of Hematology 2019;40(11):889-894
Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People's Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories' results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion: The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.
China
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Core Binding Factor Alpha 2 Subunit
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Humans
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Leukemia, Myeloid, Acute
;
RUNX1 Translocation Partner 1 Protein
;
Real-Time Polymerase Chain Reaction
;
Transcription, Genetic
;
WT1 Proteins

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