1.Identification of a JAK-STAT-miR155HG positive feedback loop in regulating natural killer (NK) cells proliferation and effector functions.
Songyang LI ; Yongjie LIU ; Xiaofeng YIN ; Yao YANG ; Xinjia LIU ; Jiaxing QIU ; Qinglan YANG ; Yana LI ; Zhiguo TAN ; Hongyan PENG ; Peiwen XIONG ; Shuting WU ; Lanlan HUANG ; Xiangyu WANG ; Sulai LIU ; Yuxing GONG ; Yuan GAO ; Lingling ZHANG ; Junping WANG ; Yafei DENG ; Zhaoyang ZHONG ; Youcai DENG
Acta Pharmaceutica Sinica B 2025;15(4):1922-1937
The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.
2.External quality assessment of prenatal screening for maternal serum inhibin A in second trimester
Yuxuan DU ; Jianming FENG ; Wei WANG ; Falin HE ; Kun ZHONG ; Shuai YUAN ; Jiali LIU ; Zhixin ZHANG ; Zhiguo WANG
Chinese Journal of Perinatal Medicine 2019;22(5):341-344
Objective To eva1uate the external quality assessment results of prenatal screening for maternal serum inhibin A in the second trimester in 2018 and to improve the accuracy of prenatal screening.Methods National Center for Clinical Laboratories provided three batches of quality control urine sample (Lot:201811-201813) to 94 prenatal screening laboratories nationwide in March 2018.Laboratories participated in the assessment voluntarily and reported the results,methods,equipment,reagents and other related information as required.Clinet EQA and Microsoft Excel 2010 were used for statistical analysis of the laboratory test results and for descriptive evaluation of the accuracy rate.Results A total of 55 laboratories submitted their testing results giving a return rate of 58.5% (55/94),of which 52 (94.5%) were consistent with the expected results,while none of the results submitted by the other three laboratories was accurate.At the mean time,the bias of all three batches in each laboratory fell into the same side (two laboratories showed negative bias and one positive bias).Conclusions The results of the external quality assessment of prenatal screening for maternal serum inhibin A are generally satisfactory except for a few laboratories.It is necessary to incorporate prenatal screening for maternal serum inhibin A in the second trimester into the formal external quality assessment plan and regularly monitor the level of its detection quality.
3.Investigation and analysis of the reference intervals for complete blood cell counting in 110 maternal and child health service centers and children's hospitals in China
Jiali LIU ; Wei WANG ; Falin HE ; Kun ZHONG ; Shuai YUAN ; Zhixin ZHANG ; Yuxuan DU ; Zhiguo WANG
Chinese Journal of Laboratory Medicine 2019;42(4):277-281
Objective To investigate and analyze the source and upper and lower limits of the reference interval of children's complete blood count in 110 maternal and child health hospitals and chil-dren's hospitals nationwide. Methods Laboratories submitted the data of reference intervals via external quality assessment (EQA) software which was based on the web. To collect the results of reference intervals questionnaires on complete blood cell counting of children in laboratory departments of 110 maternal and child care service centers and children's hospitals in China in 2017. Questionnaires include information on the source of reference intervals for 18 items of complete blood count, whether to verify, upper and lower lim-its, grouping, methods used, instruments, reagents, and calibrators. Data was analyzed using Microsoft Excel 2007 and SPSS 22.0. The median, P25, P75were obtained, and rank sum test were used to determine wheth-er there were statistical differences between groups. Results The results of 110 laboratories were obtained after rejecting invalid data. The reference intervals were mainly derived from operating procedures and the laboratories themselves, of which 50.5%-53.6% of the laboratories were validated. The white blood cell counting reference intervals gradually decreased from birth to adolescence, and the value was close to that of adults. The reference intervals of red blood cell counting and hemoglobin were close to that of adults except in the neonatal period. The value of the reference intervals of hematocrit slightly decreased with age. The dif-ference between RBC, Hgb, HCT in reference intervals between groups was statistically significant when grouped by gender(P<0.05). The reference intervals of white blood cell counting were less grouped by gender (5 laboratories), and the difference among groups was not statistically significant. There were no statistically significant differences in the reference intervals of elements between the two measurement systems that Sys-mex XN series and Sysmex XS-800i/XS-1000i/XS 500i/XS 900i series. Conclusions The establishment of reference intervals for children's complete blood cell counting was urgently needed. The reference inter-vals of the complete blood cell counting item had statistical significance in both age and gender. It was sug-gested that the industry standard of children's complete blood cell counting reference intervals should be es-tablished based on age and gender.
4.Analysis of survey for implementation of professional standards of reference intervals in routine biochemistry laboratories
Wei WANG ; Tingting LI ; Haijian ZHAO ; Falin HE ; Kun ZHONG ; Shuai YUAN ; Zhiguo WANG
Chinese Journal of Clinical Laboratory Science 2018;36(3):221-226
Objective To investigate the implementation of professional standards for reference intervals in routine biochemistry laboratories.Methods The relevant data of reference intervals from different laboratories including upper and lower limits,sources of reference intervals,verification and grouping rules,etc was submitted by using the software of interval quality assessment (EQA) via WEB application.The background monitor saved all the data as Microsoft Excel 2007 documents.The implementation of reference intervals of professional standards for decreed 18 routine biochemical tests was analyzed.Results The proportion of laboratories in which the reference intervals were derived from professional standards increased largely in 2016 compared with those in 2014.The data of 2016 showed that the reference intervals derived from professional standards were verified in 58.9% to 67.5% of laboratories before they were used in clinical diagnosis.The grouping rules for reference intervals in most laboratories (59.1% to 83.3%) were in accordance with professional standards,except for individual items,including urea (43.4%),creatinine (40.1%) and alkaline phosphatase (35.8%).There were significant differences for the upper and lower limits of the most items between the laboratories using professional standards and those without using professional standards (P < 0.05),except for some items,including lower limit value of kalium,upper limit of phosphorus,upper limit of amylase,upper limit of aspartate aminotransferase and lower limit of ferrum.There was no significant difference in most items between the the upper and lower limits of the reference intervals in the laboratories using professional standards and the reference intervals defined by professional standards,except for individual items,including upper limit of total protein,lower and upper limit of creatine kinase,upper limit of urea and upper limit of creatinine (P < 0.05).Conclusion The implementation of reference intervals from professional standards in most routine biochemistry laboratories could not be satisfactory.Only a small part of laboratories used the professional standards,and the reference intervals of professional standards,were not verified before use in quite a part of laboratories.
5.National survey of blood specimen acceptability for clinical chemistry tests in 2017
Yuanyuan YE ; Wei WANG ; Haijian ZHAO ; Falin HE ; Kun ZHONG ; Shuai YUAN ; Yuxuan DU ; Bingquan CHEN ; Zhiguo WANG
Chinese Journal of Clinical Laboratory Science 2018;36(6):467-471
Objective To investigate the status of blood specimen acceptability for clinical chemistry tests in routine medical laboratories of China. Methods The questionnaires were assigned to the laboratories which participated in the routine chemistry exter-nal quality assessment (EQA) programs proposed by National Health Commission for Clinical Laboratory. The questionnaires included general information of participants and information about unacceptable blood specimens. Participants were required to record all the in-formation concerning unacceptable blood specimen received from 1stto 31stJuly, 2017. The data from each laboratory were reported and collected via special online system.Results A total of 866 valid questionnaires were collected.Of 15 981 752 specimens received dur-ing the data collection period unqualified 122 00 specimens were rejected with overall rejection rate of 0.076%. The main reasons for unacceptable specimens were hemolysis (33.98%), insufficient specimen quantity (10.78%) and chylemia/lipemia (10.62%). The rejected specimens were related to the original laboratories, types of container and specimen, transportation manner and operating staff of blood collection. Conclusion Certain problems existed in the receiving and management system for unqualified blood specimen in our country and remaining to be perfected. The clinical laboratories should pay more attention for pre-examination stage, including routinely monitoring unacceptable specimens, analyzing related data at the most possible granular levels, identifying the main problem and taking effective measures.
6.External quality survey results of newborn hemoglobinopathy in China
Yuxuan DU ; Shuodan HUANG ; Jie ZOU ; Jingyun HUANG ; Wei WANG ; Falin HE ; Kun ZHONG ; Shuai YUAN ; Zhiguo WANG
Chinese Journal of Laboratory Medicine 2018;41(6):466-469
Objective To evaluate the results of 2017 external quality assessment for newborn hemoglobinopathyand improve the quality of disease screening .Methods Each of 26 participating laboratories testing newborn hemoglobinopathy across the country received 5 batches of quality control blood spots ( Lot 201711-201715 ) in octorber 2017.Laboratories voluntarily participated in the survey and reported the results, methods, equipments and reagents information .Clinet EQA, and Microsoft Excel 2010 were used to perform statistical analysis on the laboratory test results .The rates of accuracy ( number of correct results/total number of submitted results ) were used for evaluating the performance of laboratories . Results 24 laboratories submitted the testing results with a return rate of 80.8%(21/26).The rates of accuracy for each lot were 100%(21/21), 90.5%(19/21), 90.5%(19/21), 57.1%(12/21) and 100%(21/21 ) respectively.Conclusions The results of this external quality assessment for newborn hemoglobinopathy is generally satisfactory , except for HbBarts′and HbA2.The screening laboratories should improve their quality control system , take timely measures to correct mistakes during the analytic period and improve the accuracy of screening tests for newborn hemoglobinopathy.
7.Quality Control of Preanalytical Variations for the Determination of Trace Element Aluminum, Arsenic,Chromium, Cadmium and Mercury in Samples of Human Origin
Kun ZHONG ; Wei WANG ; Falin HE ; Shuai YUAN ; Zhiguo WANG
Journal of Modern Laboratory Medicine 2017;32(2):160-164
The aims of this article is to provide the quality control requirements of preanalytical variation for the determination of trace element aluminum,arsenic,chromium,cadmium and mercury in samples of human origin,reduce the influence of preanalytical variation on the test results.Refer to the Clinical and Laboratory Standards Institute (CLSI) documents,Control of Preanalytical Variation in Trace Element Determinations and other references and guidelines,the methods of quality control of aluminum,arsenic,chromium,cadmium and mercury determination have been made,including:the factors needed to be considered in collection,preservation,transportation and other preanalytical factors,the abilities and considerations of laboratory staff,etc.Hope this article provide some useful suggestions and help to the laboratories of determination of aluminum,arsenic,chromium,cadmium and mercury in samples of human origin.
8.Survey and Analysis for Maternal Serum Marker of Prenatal Screening in Second Trimester in 2 0 1 5
Falin HE ; Wei WANG ; Kun ZHONG ; Shuai YUAN ; Zhiguo WANG
Journal of Modern Laboratory Medicine 2017;32(1):154-156,164
Objective To investigate the dates of 477 Chinese prenatal screening centers for previous half year analyse prena-tal screening status and provide recommendations for quality control.Methods All China prenatal screening centers were sent the data via the National Quality Assessment Scheme.This covered the software used,the risk cut-offs,monthly sample throughput,monthly median MoM of AFP,hCG,β-HCG,freeβ-HCG and uE3,monthly screening positive rate for trisomy 21,trisomy 18 and Open Neural Tube Defect.Results Screening protocol were versatile,with 73.48% (133/181)used two-marker model,24.31% (44/181)used three-marker model and 2.21% used four-marker model.About the software used, 350 laboratories never updated the screening parameters,89 laboratories had updated their median or parameter by manufac-turers,24 laboratories had updated the parameters by themselves.Cut-offs differed between laboratories.59.91% (275/459) used 1/270 as their cutoffs for trisomy 21.66.22% (296/447)used 1/350 as their cutoff for trisomy 18 and 96.52% (361/374)used cutoffs between 2.0~2.5 MOM for ONTD.Results of monthly median MOM:the percentage of laboratories that all six monthly median MOM within the target of 0.90~1.10 was 46.69% (155/332)for AFP,20.0% (4/20)for hCG, 29.17% (28/96)forβ-HCG,15.66% (31/198)for freeβ-HCG and 4.82% (11/228)for uE3.The percentage of laborato-ries that all six monthly median MOM within the target of 0.95~1.05 was 14.16% (47/332)for AFP,0% (0/20)for hCG,4.17% (4/96)forβ-HCG,12.63% (25/198)for freeβ-HCG and 4.82% (11/228)for uE3.About screening positive rate,there were difference of trisomy 2 1 positive rate in the same laboratory within the six month.Conclusion There were variations types of screening protocol,different kinds of soft platform,randomness of choice or update of medians or other important parameters and great difference in awareness of quality control.It would be taken effective and practical quality control measures to help laboratories improve quality control.
9.Analysis and Comparison of Reference Intervals of Serum Total Bilirubin and Serum Direct Bilirubin with Upcoming Industry Standards in China
Shishi ZHANG ; Wei WANG ; Haijian ZHAO ; Falin HE ; Kun ZHONG ; Zhiguo WANG
Journal of Modern Laboratory Medicine 2017;32(3):152-156
Objective To analyze the reference intervals of serum total bilirubin (TBIL) and serum direct bilirubin (DBIL) by all Chinese clinical laboratories and make a comparison with the upcoming part 4 of Industry Standard WS/T 404.Methods Relevant information about reference intervals of all clinical laboratories participating in TBIL and DBIL testing items of 2014 national external quality assessment scheme of clinical routine chemistry was collected by a web-based external quality assessment software,including source,grouping,verification,upper and lower limits of reference intervals and instruments,reagents,methods and calibrators used.Microsoft Excel 2010 and SPSS 19.0 were applied to statistical analysis.The comparison between reference intervals used and the upcoming Industry Standard was conducted by the simple mean t test.Laboratories derived from the highest percentage of source distribution whose reagent and instrument were matching with each other were grouped according to the test systems used and the differences of reference intervals between three mainly used test systems and the upcoming Industry Standard were also compared with the single sample mean t test.Results The number of laboratories participated in the investigation about source distribution of reference intervals for TBIL and DBIL was 749 and 709 respectively.For these two items,the highest sources were both instructions of reagent(TBIL 58.08%,DBIL 58.67 %),next were both National Clinical Laboratory Operation Rules (3rd Edition) (TBIL 29.64 %,DBIL 28.91 %),the percentages of other sources were all less than 10%.Besides,there were respectively 379 (50.60%) and 354 (49.93%) laboratories verifying their reference intervals for TBIL and DBIL.The difference of the comparison between reference intervals used and the upcoming Industry Standard had statistical significance (P<0.05).The using reference intervals were narrower than the upcoming Industry Standard for both items.In all laboratories with reference intervals from instructions of reagent,themating laboratories respectively accounted for 41.88% and 41.48%% for item TBIL and DBIL.As the single sample mean t test showed,the comparison of the reference intervals between three mainly used test systems in these mating laboratories and the upcoming Industry Standard had statistical significance (P<0.05),except for the lower limit of DBIL with Beckman test system (P value was 0.068) and the upper limit of DBIL with HITACHI test system (P value was 0.087).Conclusion Currently,the using situation of reference intervals about TBIL and DBIL by all Chinese laboratories was not scientific and rational enough and has significant difference with the upcoming Industry Standard.Should publish the part 4 of Industry Standard WS/T 404 as soon as possible,which would help clinical laboratories establishing suitable reference intervals and promote the standardization of its usage.
10.Investigation and Analysis of Reference Intervals and Decision Limits of Reticulocyte Count in China
Xiaoyan ZHANG ; Wei WANG ; Falin HE ; Kun ZHONG ; Zhiguo WANG
Journal of Modern Laboratory Medicine 2016;31(3):158-161
Objective To investigate and analyze the current situation of reference intervals and decision limits of reticulocyte count in China.Methods The information related to upper/lower limits,decision limits,data resources,method principles, instruments and reagents of reticulocyte count in 2014 was collected via the external quality assessment software system based on website.The participants were divided according to their methods and instruments.The SPSS 1 9.0 was used for conducting the data analysis and statistics of results for each group.Results There were 276 laboratories submitting the val-id results.The major resources for reference intervals came from national guide to clinical laboratory procedures (53.99%), instructions of instrument manufacturers (16.30%),textbook (9.78%),instructions of reagents manufacturers (9.06%) and others.The major resources for decision limits were national guide to clinical laboratory procedures (56.06%),instruc-tions of instrument manufacturers (16.67%),textbook (7.58),instructions of reagents manufacturers (7.58%)and others. The medians and averages of upper/lower limits and decision limits among subgroups were close,whereas the P2.5 and P97.5 were significant discrepancies.Only 45.65% and 48.48% of participant laboratories had verified reference intervals and deci-sion limits before clinic use.The lower limits and decision limits among subgroups had nostatistical difference (P>0.05), where as the upper limits of different instrument groups had significant differences (P<0.001).Conclusion The current situation of reference intervals and decision limits of reticulocyte count is unsatisfactory.It is certain to establish a uniformed reference interval and decision limits for reticulocyte count,which provides a reference for the standardization of reticulocyte count testing.

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