Table of Content

30 October 2022, Volume 37 Issue 10

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Interpretation and application of 15 quality control indicators in clinical laboratories

KAN Lijuan, ZHANG Lijun, ZHANG Xiuming

2022, 37(10):  907-914.  DOI: 10.3969/j.issn.1673-8640.2022.010.001

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The quality control indicators of clinical laboratories are essential in clinical laboratories as they enable the management to evaluate their performance objectively. As mentioned in the National Tertiary Public Hospitals Performance Evaluation Operational Manual （2022 edition），quality control indicators have been combined into performance appraisal system. Although 15 indicators from the Quality Control Indicators in Clinical Laboratory Service （2015） published by the National Health and Family Planning Commission，which are adopted in this manual，the interpretation of these indicators，the concepts of denominator and the numerator in the equations，as well as the datum acquisition methods are inconsistent，which leads to inaccurate results in performance evaluations between laboratories. This review makes the practice-based suggestions and opinions on interpreting and applying the 15 quality control indicators in clinical laboratories.

Expressions of sLAIR-1 and LAIR-1 mRNA in AS patients and their relationship with disease activity

HE Yaya, CHEN Shanshan, LI Yongsheng, LIU Juan

2022, 37(10):  915-920.  DOI: 10.3969/j.issn.1673-8640.2022.010.002

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Objective To investigate the changes of serum soluble leukocyte-associated immunoglobulin-like receptor-1（LAIR-1）（sLAIR-1） and LAIR-1 mRNA in peripheral blood mononuclear cells（PBMC） of patients with ankylosing spondylitis（AS） and their relationship with disease activity. Methods Totally，81 patients with AS were enrolled as AS group，and another 80 healthy subjects were enrolled as control group. The patients' clinical data and routine laboratory determination results were recorded. Serum sLAIR-1，interleukin（IL）-6 and IL-17 levels were determined，and the relative expression of LAIR-1 mRNA was determined as well. The difference between AS and control groups was compared. LAIR-1 and LAIR-1 mRNA levels were also determined in 17 patients with active AS of the 81 AS patients after 6 weeks of infliximab treatment. The correlations between sLAIR-1 and LAIR-1mRNA and the other indicators were analyzed by Spearman correlation analysis. Results Serum sLAIR-1，IL-17 and IL-6 in AS group were higher than those in control group（P<0.001），while LAIR-1 mRNA levels in AS group were lower（P<0.001）. Spearman correlation analysis showed that sLAIR-1 was positively correlated with IL-17，IL-6 and C-reactive protein（CRP）（r values were 0.482 4，0.475 3 and 0.391 6，respectively，P<0.01） and with the ankylosing spondylitis disease activity score（ASDAS） with CRP（ASDAS-CRP）（r value was 0.565 7，P<0.01），while LAIR-1 mRNA was negatively correlated with SLAIR-1， IL-17，IL-6，CRP and ASDAS-CRP（r values were -0.446 6，-0.399 6，-0.227 8，-0.265 1 and -0.366 8，respectively，P<0.05）. Serum sLAIR-1 was decreased（P<0.05），and LAIR-1 mRNA was increased（P<0.05） in patients with active AS after 6 weeks of infliximab treatment. Conclusions LAIR-1 was closely related to the disease activity，indicating that it may be used as a new indicator for the evaluation of AS disease activity.

Role of line chart model based on peripheral blood-derived inflammation markers in early diagnosis of neonatal septicemia

HE Xuelian, HE Ziyi, LIU Yueyang, YU Yanzhi, ZHANG Siying

2022, 37(10):  921-927.  DOI: 10.3969/j.issn.1673-8640.2022.010.003

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Objective To establish and evaluate a line chart model for the early diagnosis of neonatal septicemia by using peripheral blood-derived inflammation markers. Methods Totally，137 patients with neonatal septicemia and 114 non-infected newborns were enrolled，96 cases of neonatal septicemia patients were randomly selected as septicemia group，96 cases of non-infected newborns were selected as control group，and the remaining 59 newborns（41 cases of neonatal septicemia patients and 18 cases of non-infected newborns） were included in model verification group. The clinical data of all the newborns were collected，blood routine tests were performed，and the test items included white blood cell（WBC） count，hemoglobin（Hb），platelet（PLT） count，lymphocyte percentage（LYMPH%），neutrophil percentage（NEUT%），hematocrit（HCT），C-reactive protein（CRP），procalcitonin（PCT） and interleukin-6（IL-6）. Logistic regression analysis was used to evaluate the risk factors of neonatal septicemia，and a line chart model was constructed. Receiver operating characteristic（ROC） curve，decision curve and calibration curve were used to evaluate and validate the model. Kaplan-Meier survival curve was used to evaluate the probability of neonatal septicemia in different risk groups. Results There was statistical significance in WBC count，PLT count，Hb，NEUT%，CRP，PCT and IL-6 between septicemia group and control group（P<0.05），but there was no statistical significance in LYMPH% and HCT（P>0.05）. The results of Logistic regression analysis showed that the elevated levels of CRP，PCT and IL-6 were risk factors for neonatal septicemia [odds ratios（OR） were 2.943，2.862 and 2.915，respectively，P<0.05]. The total score of risk factors in the line chart was 239.78，and the corresponding incidence of neonatal septicemia was 71.86%. The C-index value of the line chart diagnosis model for neonatal septicemia was 0.934，the area under curve was 0.831，the sensitivity was 82.1%，and the specificity was 80.4%. The ideal curve in the calibration curve was close to the actual curve，the accuracy was good，the area under decision curve was 0.792，and the clinical net benefit rate of the model was high. According to the critical value of the line chart diagnosis model score，the occurrence probability of neonatal septicemia was classified into 3 groups，low risk（≤83.65），medium risk（>83.65-≤157.89） and high risk（>157.89） groups. The probability of neonatal septicemia was 29.47%，45.57% and 83.33%，respectively. Conclusions The line chart diagnosis model based on CRP，PCT and IL-6 is of value in early diagnosis of neonatal septicemia.

Role of the prenatal diagnosis of SRPS-5 neonate caused by compound heterozygous mutation of WDR35 by Trio-WES

ZHAO Xuliang, TIAN Ruixia, SHI Youwen, YU Min, JIAO Liuliu, ZHU Fuxi

2022, 37(10):  928-933.  DOI: 10.3969/j.issn.1673-8640.2022.010.004

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Objective To investigate the role of prenatal diagnosis of a neonate of short-rib polydactyly syndrome-5（SRPS-5） induced by a compound heterozygous mutation of WDR35 by trio-whole exome sequencing （trio-WES）. Methods The clinical data of prenatal diagnosis of a neonate were collected. The genes of induced labor tissues and parents were determined by trio-WES. The biohazard analysis of the suspicious variant was carried out by using SIFT，PolyPhen-2 and Mutation Taster software，and the model was established to predict the protein structure changes caused by the mutation. Results At 22⁺³ weeks of gestation，ultrasound examination showed that fetal limb long bone had developmental delay，with bilateral humerus and femur bending，narrow chest cavity and reduced chest circumference，shortened ribs and compressed lungs. The gene test showed that there were compound heterozygous mutations in WDR35 in fetus，which were heterozygous mutation in father（c.799G>A/p.Val267Met） and loss of heterozygous mutation in chr2：20151176-2015124 in mother. The 2 mutations searched from PubMed and HGMD databases had not been reported. There were new mutations of WDR35. The c.799G>A/p.Val267Met was highly conserved among species，and the prediction of protein structure suggested that it might change the local spatial stability. Conclusions The defect of WDR35 may be the pathogenic factor of the fetal long bone shortening with bending，short rib with lung dysplasia and other symptoms，and the accurate diagnosis of SRPS-5 can be made by trio-WES.

Evaluation of MCP-1 combined with CREWS for poor prognosis in patients with AECOPD

WANG Xiaoqing, PENG Xuemei, LAN Meifeng, PAN Min

2022, 37(10):  934-938.  DOI: 10.3969/j.issn.1673-8640.2022.010.005

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Objective To investigate the effect of monocyte chemotactic protein-1（MCP-1） and chronic respiratory early warning score（CREWS） on predicting acute exacerbations of chronic obstructive pulmonary disease（AECOPD） poor prognosis. Methods A total of 260 patients with AECOPD were enrolled. MCP-1 level at admission was determined，and CREWS was performed simultaneously. According to the prognosis during hospitalization and within 1 year after discharge，they were classified into poor prognosis group and good prognosis group. Multivariate Cox regression analysis was used to evaluate the risk factors for poor prognosis in patients with AECOPD. Receiver operating characteristic（ROC） curve was used to evaluate the efficacy of each index in predicting poor prognosis（readmission or death） in patients with AECOPD. Kaplan-Meier survival curve was used to evaluate the survival of AECOPD patients. Results The proportion of pulmonary function grade Ⅲ-Ⅳ，MCP-1 level and CREWS in poor prognosis group were higher than those in good prognosis group（P<0.05），but there was no statistical significance in the other indicators between the 2 groups（P>0.05）. Multivariate Cox regression analysis showed that pulmonary function grade，MCP-1 and CREWS were risk factors for poor prognosis in patients with AECOPD [odds ratios（OR） were 3.045，1.683 and 1.423，respectively，95% confidence intervals（CI） were 1.467-4.638，1.132-4.248 and 1.138-1.865，respectively]. ROC curve analysis showed that the areas under curves（AUC） of MCP-1 and CREWS single determinations and combined determination for predicting poor prognosis（readmission or death） of AECOPD patients were 0.823，0.881 and 0.912，respectively，and the optimal cut-off values of MCP-1 and CREWS were 42.19 ng/L，6 and 0.48，respectively. AECOPD patients with CREWS<6 and MCP-1<42.19 ng/L were classified into low-risk group（78 cases），and AECOPD patients with CREWS≥6 and MCP-1≥42.19 ng/L were classified into high-risk group（87 cases），and the remaining AECOPD patients were classified into medium-risk group（95 cases）. The event free survival rate in high-risk group was lower than those in low-risk and medium-risk groups（P<0.001）. Conclusions MCP-1 level and CREWS have certain predictive value for poor prognosis of AECOPD patients.

Clinical value of serum lipoprotein-related phospholipase A2 combined with superoxide dismutase in predicting mild cognitive impairment in cerebral small vessel disease patients

MAN Chunlu, YANG Qingsong

2022, 37(10):  939-943.  DOI: 10.3969/j.issn.1673-8640.2022.010.06

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Objective To evaluate the clinical value of serum lipoprotein-related phospholipase A2（Lp-PLA2） combined with superoxide dismutase（SOD） in predicting mild cognitive impairment （MCI）in cerebral small vessel disease（CSVD）. Methods According to the Montreal Cognitive Assessment（MoCA） score at admission，a total of 120 patients with CSVD were enrolled and classified into MCI group（MoCA score <26） and control group（MoCA score ≥26）. The general information and past medical history of the patients were collected，and plasma Lp-PLA2 and SOD levels were determined. Pearson correlation analysis was used to evaluate the correlation between Lp-PLA2，SOD and MoCA score. Multivariate Logistic regression analysis was used to evaluate the risk factors for MCI. Receiver operating characteristic（ROC） curve was used to evaluate the values of Lp-PLA2 and SOD in the auxiliary diagnosis of MCI. Results The level of Lp-PLA2 in MCI group was higher than that in control group（P<0.05），and the level of SOD was lower than that in control group（P<0.05）. Multivariate Logistic regression analysis showed that Lp-PLA2 [odds ratio（OR）=3.241，95% confidence interval（CI） 2.014-5.362] were independent risks of MCI，and SOD（OR=0.652，95%CI 0.407-0.964） was an independent protective factor for MCI. Lp-PLA2 was negatively correlated with MoCA score（r=-0.535，P=0.017），and SOD was positively correlated with MoCA score（r=0.684，P=0.008）. The areas under curves（AUC） of Lp-PLA2，SOD single determinations and combined determination in the diagnosis of MCI were 0.813，0.738 and 0.903，respectively，and the efficiency of combined determination was better than those of single determinations（P<0.05）. Conclusions Lp-PLA2 and SOD are influence factors for MCI in CSVD patients，and the combined determination may play a role in the diagnosis of MCI.

Roles of MxA，CRP and WBC count in the differential diagnosis of acute respiratory tract viral and bacterial infections

LIU Chunxiao, YI Changlin, WANG Xiaoshan, ZHU Yongzhen, LUO Aner, CHEN Changqiang

2022, 37(10):  944-947.  DOI: 10.3969/j.issn.1673-8640.2022.010.007

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Objective To investigate the clinical application values of myxovirus resistance protein A（MxA），C-reactive protein（CRP） and white blood cell（WBC） count in the differential diagnosis of acute respiratory tract viral infection and bacterial infection. Methods The viral infection group（350 cases），bacterial infection group（244 cases） and healthy control group（100 cases） were enrolled for determining MxA，CRP and WBC count. The diagnostic efficacy of the 3 indexes in each group was analyzed by receiver operating characteristic（ROC） curve. Results The MxA level in viral infection group was higher than those in bacterial infection group and healthy control group（P<0.05，P<0.01），and that in bacterial infection group was higher than that in healthy control group（P<0.05）. The CRP level and WBC count were higher in bacterial infection group than those in viral infection group and healthy control group（P<0.05，P<0.01），and that in viral infection group was higher than that in healthy control group（P<0.05）. ROC curve analysis showed that the areas under curves（AUC） of MxA，CRP，WBC count single determinations and combined determination were 0.829，0.703，0.665 and 0.850 for the differential diagnosis of viral infection and bacterial infection，respectively. The differential diagnostic performance of combined determination was better than those of single determinations（P<0.01）. Conclusions MxA，CRP and WBC count have good clinical application value in acute respiratory tract infectious diseases. MxA is superior to CRP and WBC count in distinguishing viral infection and bacterial infection，and the differential diagnostic performance of combined determination is better.

Establishment and evaluation of α-thalassemia and β-thalassemia mutation determinations using hetero-tail dual-labeled fluorescent probe hydridization

LI Renqiang, LUO Junfeng, CHEN Yundi

2022, 37(10):  955-962.  DOI: 10.3969/j.issn.1673-8640.2022.010.010

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Objective To establish and evaluate a method for determining 3 α-thalassemia non-deletional mutations（αWS，αQS，αCS） and 8 β-thalassemia point mutations [CD26（G>A），CD41/42（-TCTT）， nt29（A>G） ， IVS-Ⅱ-654（C>T）， nt28（A>G） ， CD71/72（+A） ，CD17（A>T）， CD27/28（+C）] simultaneously using hetero-tail dual-labeled fluorescent probe hydridization. Methods Polymerase chain reaction（PCR） primers and hetero-tail dual-labeled fluorescent probes targeting 11 most common α-thalassemia non-deletional and β-thalassemia point mutations were designed. An optimized multiplex asymmetric PCR and hetero-tail dual-labeled fluorescent probe hydridization were established. Performance specifications（accuracy，specificity and sensitivity） were evaluated by the national reference materials for thalassemia. Totally，200 clinical samples were determined by PCR-reverse dot blot kit and hetero-tail dual-labeled fluorescent probe hydridization concurrently to assess the consistency. Results For 11 mutations within the determination range，hetero-tail dual-labeled fluorescent probe hydridization showed 100% consistency with the national reference materials for thalassemia，and none of the mutations outside the determination range were determined. For different concentrations of Hb CS，CD41/42 and IVS-Ⅱ-654 reference materials ranging from 1.0，2.5，5.0 to 10.0 ng/μL，the results were consistent. The consistency rate between PCR-reverse dot blot kit and hetero-tail dual-labeled fluorescent probe hydridization was 100%. Conclusions Hetero-tail dual-labeled fluorescent probe hydridization enables fast and accurate determination of 11 α-thalassemia non-deletional and β-thalassemia point mutations simultaneously by one-step real-time PCR，which reduces turn-around time and contamination risk and shows potential for future clinical application.

Rapid identification of carbapenemase producing Enterobacteriaceae phenotypes by modified Carba Np test and mCIM/eCIM test

BAO Hailin, HUA Hongyan, SUN Hengliang, LIU Hua, JI Shunnian, QIN Chenhao, DU Hong

2022, 37(10):  963-968.  DOI: 10.3969/j.issn.1673-8640.2022.010.011

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Objective To evaluate the application value of modified Carba Np test and modified carbapenem inactivation method（mCIM），ethylenediaminetetraacetic acid-carbapenem inactivation method（eCIM） for detecting carbapenemase producing Enterobacteriaceae phenotypes. Methods Totally，86 isolates of carbapenem resistant Enterobacteriaceae（CRE） and 50 sensitive isolates were collected. Phenotype analysis and classification were performed by modified Carba Np test and mCIM/eCIM，respectively. The carbapenemase genes were detected by polymerase chain reaction（PCR）. The difference between the 2 methods was evaluated. Results Among the 86 isolates of CRE，81 isolates were drug-resistant gene positive，and all the 50 sensitive isolates were drug-resistant gene negative. The 82 isolates of CRE were positive by modified Carba Np test，and 78 isolates were positive by mCIM/eCIM test. Compared with PCR results，the sensitivity and specificity of modified Carba Np test were 96.3% and 92.7%，respectively，the Kappa value was 0.935. The sensitivity and specificity of mCIM/eCIM test were 92.6% and 94.5%，respectively，and the Kappa value was 0.917. The detection rates of serine carbapenemase and metallocarbapenemase were 97.7% and 100.0% with modified Carba Np test. The sensitivity and specificity of mCIM/eCIM test were 91.2% and 90.4%，respectively. There was no statistical significance between modified Carba Np test and mCIM/eCIM test（χ²=1.65，P>0.05）. Conclusions The modified Carba Np test could rapidly identify the phenotypes of carbapenemase producing Enterobacteriaceae，and the modified mCIM/eCIM test is convenient，easy to operate and has few interference factors. The 2 methods could complement each other with clinical application value.

Application of Gram staining and MALDI-TOF MS in the rapid identification of pathogen kinds in children's positive blood culture

YANG Xi, SONG Wenqi, DONG Fang, MENG Qingying, ZHEN Jinghui, ZHOU Wei

2022, 37(10):  969-973.  DOI: 10.3969/j.issn.1673-8640.2022.010.012

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Objective To study the application of Gram staining and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry（MALDI-TOF MS） in the rapid identification of pathogen kinds in children's positive blood culture，and to provide a rapid and accurate laboratory reference for children's bloodstream infection. Methods The positive aerobic blood culture bottles of children submitted for clinical examination in Beijing Children's Hospital Affiliated to Capital Medical University from February 2019 to October 2020 were collected. Gram staining microscopy，rapid identification of MALDI-TOF MS and culture were carried out. Based on the identification results after culture，the effect of Gram staining and rapid identification of MALDI-TOF MS was evaluated. Results A total of 166 positive samples of children's aerobic blood culture were collected，of which 97.6% （162/166） were single bacteria，and 2.4%（4/166） were multiple bacteria. According to the identification results after culture，the coincidence rate of Gram staining microscopy in 162 single bacterium samples was 97.5%（158/162），of which the coincidence rate of Gram-positive bacteria was 97.9%（93/95），Gram-negative bacteria was 96.8%（61/63），and the coincidence rate of yeast like fungi was 100.0%（4/4）. The coincidence rate of rapid identification by MALDI-TOF MS was 85.2%（138/162），including 81.1% （77/95） of Gram-positive bacteria，92.1%（58/63） of Gram-negative bacteria and 75.0%（3/4） of yeast like fungi. Among the 4 2-kind bacteria samples，the results of Gram staining microscopy were consistent with those after culture，and only one of them could be identified by MALDI-TOF MS. The coincidence rate of rapid identification of Gram-negative bacteria by MALDI-TOF MS was higher than that of Gram-positive bacteria（P>0.05）. When time to positivity（TTP）< 21 h，the coincidence rate of MALDI-TOF MS was higher，especially for Gram-negative bacteria（P<0.05）. Conclusions Gram staining and MALDI-TOF MS can rapidly identify the pathogens in children's positive blood culture in a short time，so as to provide a rapid and accurate laboratory reference for clinical diagnosis and treatment of children's bloodstream infection，and to reduce the hospitalization cost and mortality of bloodstream infection in children.

Comparison of EUCAST and CLSI broth microdilution methods for the susceptibility testing against Candida albicans

ZHANG Yaru, LING Liyan, CHEN Min

2022, 37(10):  974-978.  DOI: 10.3969/j.issn.1673-8640.2022.010.013

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Objective To compare the results of susceptibility testing by European Committee on Antimicrobial Susceptibility Testing（EUCAST） and the Clinical and Laboratory Standards Institute（CLSI） broth microdilution methods against Candida albicans. Methods The susceptibilities of 42 isolates of Candida albicans were determined for amphotericin B，anidulafungin，caspofungin，fluconazole，itraconazole，voriconazole，posaconazole and micafungin according to EUCAST and CLSI methods. The essential agreement（EA），categorical agreement（CA），very major errors（VME） and major errors（ME）of the 2 methods were compared. Results The EA was 95.2%-100.0%. The CA，ME and VWE were 95.2%-100.0%，0%-4.8% and 0%-2.4%，respectively. The ME for fluconazole was 4.8%，and the VME for posaconazole was 2.4%. Conclusions The results of susceptibility testing by EUCAST and CLSI broth microdilution methods are comparable against Candida albicans. There are several areas where additional steps toward harmonization are warranted.

Influence of MUC16 on the cell proliferation and invasion of osteosarcoma cells

LI Mingwu, WANG Qinzhi, SUN Farui

2022, 37(10):  979-983.  DOI: 10.3969/j.issn.1673-8640.2022.010.014

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Objective To investigate the influence of mucin 16（MUC16） on the proliferation and invasion of human osteosarcoma cell line U2OS. Methods The U2OS cells were classified into sh-MUC16 group（transfected with MUC16 interference sequence），sh-Control group（transfected with negative control sequence） and blank group（without any treatment）. Real-time fluorescence quantitative polymerase chain reaction（PCR） was used to determine the expression of MUC16 mRNA in each group，methyl thiazolyl tetrazolium（MTT） method was used to determine cell proliferation activity，Transwell method was used to determine cell migration and invasion ability，and western blotting was used to determine the expressions of MUC16 epithelial E-cadherin（E-Cad） and neuropathic cadherin（N-Cad） in cells. Results The relative expression level of MUC16 mRNA in sh-MUC16 group were lower than those in sh-Control group and blank group（P<0.05），while there was no statistical significance between sh-Control group and blank group（P>0.05）. The cell proliferation activities in sh-MUC16 group at 24，48，72 and 96 h were lower than those in sh-Control group and blank group（P<0.05）. The number of migrating and invasive cells in sh-MUC16 group were lower than those in sh-Control group and blank group（P<0.05）. The relative expression levels of MUC16 and N-Cad in sh-MUC16 group were lower than those in sh-Control group and blank group，while the relative expression level of E-Cad was higher than those in sh-Control group and blank group（P<0.05）. Conclusions Silencing the expression of MUC16 gene in U2OS cells can inhibit cell proliferation activity，cell migration and invasion，and its mechanism may be related to the inhibition of epithelial-mesenchymal transition.

Optimization of serum uric acid reference measurement proceduce and application in conventional systems

SUN Jiangman, MENG Xiangzhao, LI Min, SHAO Yan, YU Hongyuan

2022, 37(10):  984-988.  DOI: 10.3969/j.issn.1673-8640.2022.010.015

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Objective To optimize serum uric acid reference measurement produce（reference method），and to provide a reference for the establishment of conventional systems. Methods The reference methods of serum uric acid recommended by American Association for Clinical Chemistry（AACC） were established and optimized（centrifugation for 40 min and recentrifugation for 15 min），and accuracy verification was performed by the National Institute of Standards and Technology（NIST）standard reference method（SRM） 909C and RELA20B，RELA21A. High，medium and low clinical residual serum samples were collected，and each concentration value was measured for precision verification. Totally，6 concentration gradients were configured for linear evaluation. The optimized reference method and clinical conventional method were used to measure 40 individual serum samples simultaneously，and the results of the 2 methods were analyzed by regression analysis. According to the Clinical and Laboratory Standards Insititute（CLSI） EP14-A3，interchangeability analysis of calibrators used in conventional methods was performed. Results The results of SRM 909C，RELA20B and RELA21A measured before and after the optimization of reference method were all within the equivalent limit of the International Federation of Clinical Chemistry and Laboratory Medicine（IFCC）（3.25%），and the results of SRM 909C before and after the optimization were also within the certificate range [（278.57±5.95） μmol/L]. After optimization，the repeatability precision was improved obviously. Although the repeatability precision was not improved obviously，the low-value precision was improved，and it met the precision requirement of laboratory [coefficient of variation（CV）<2%]. The optimized linear correlation（r²=0.999 9）was good，the slope was closer to 1，and the intercept was closer to 0. The expected biases of conventional method at medically determined levels 110，480 and 640 μmol/L were -15.86%，-2.03% and -1.01%，respectively. The 2 calibrators exceeded the 95% confidence interval，so there was no interchangeability between the reference method and the conventional method. Conclusions The optimized serum uric acid reference method has good precision and linear correlation，which can provide a reference for the establishment and traceability of clinical conventional measurement procedure.

Research progress on the drug resistance mechanism of clinical pathogens to fosfomycin

WANG Lixin, SU Yunfu, WANG Yi

2022, 37(10):  993-997.  DOI: 10.3969/j.issn.1673-8640.2022.010.017

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With the spread of multidrug-resistant or extensively drug resistant pathogens and the lack of new antibiotics，many old antibiotics，such as fosfomycin and polymyxin，are reused for anti-infection treatment in clinic. Fosfomycin has a unique mechanism against Gram-positive and Gram-negative bacteria. Cross-resistance is not common. This review mainly focuses on drug resistance mechanism to fosfomycin，such as drug resistance caused by murA mutations，mutations in the chromosomal genes encoding fosfomycin transporters，acquisition of plasmid-encoded genes encoding fosfomycin-modifying enzymes and hetero-resistance to fosfomycin.