Development and management of clinical mass spectrometry in laboratory medicine / 中华检验医学杂志

Clinical mass spectrometry plays an increasingly important role in the analysis of hormones, drugs, vitamins, amino acids,etc. The analysis of large molecular peptides and proteins by mass spectrometry has also attracted wide attention. The development of clinical mass spectrometry technology still faces many challenges. With continuous efforts, clinical mass spectrometry technology will have a better future.

Liver failure with green neutrophilic inclusions after liver transplantation: a case report / 中华检验医学杂志

We report a case of a 44-year-old female patient with acute liver failure and hepatic encephalopathy. The patient received artificial liver treatment and underwent allogeneic orthotopic liver transplantation at 14 days after admission. Laboratory examination reported a small number of green cytoplasmic inclusions in neutrophils on the peripheral blood smear at 68 days after admission. The patient eventually died of liver failure at 71 days after admission. Green inclusions are bright green or blue-green inclusions presented in the cytoplasm of neutrophils in Wright-Giemsa stained peripheral blood smears, and is associated with liver failure and high short-term mortality.

Attention should be given to the research and development of laboratory medicine in the field of cardiovascular metabolism / 中华检验医学杂志

Cardiometabolic disease mainly refers to the cardiovascular disease caused by the increased metabolic burden, including hypertension, diabetes, dyslipidemia, coronary heart disease, stroke, and so on. In China, the incidence of this kind of disease is continuous rising, and cardiometabolic disease is more and more diagnosed in patients in younger age. Currently, continuous exploration of new biomarkers and detection methods, standardization of testing techniques, strengthening of clinical and laboratory communication and cooperation, and cultivation of interdisciplinary talents are the major focuses in term of promoting the development of laboratory medicine in the field of cardiovascular metabolism.

Clinical significance of loss of chromosome Y in patients with multiple myeloma / 中华检验医学杂志

Objective:To explore the risk stratification and prognostic significance of loss of chromosome Y (LOY) in patients with multiple myeloma (MM).Methods:The clinical data of 193 male patients with newly diagnosed MM admitted to Zhongshan Hospital of Fudan University from January 2018 to January 2020 were analyzed retrospectively and divided into a normal karyotype group(178) and a LOY karyotype group (15) according to the results of their primary conventional cytogenetics. Rank sum test, 2×2 chi-square test and independent sample t-test were used to compare laboratory findings, such as liver and kidney function, immunohistochemistry and cytogenetics, treatment efficacy and survival prognosis, between the two groups. The clinical prognostic significance of LOY was summarized through survival analysis and Cox regression. Results:Among the newly diagnosed male MM patients, 8%(15/178) were confirmed with LOY cases. The proportion of patients with Revised International Staging System(R-ISS) stage Ⅲ was significantly higher in the LOY group (8/15) than that in the normal karyotype group (40/178)(χ 2=7.052, P<0.01). A higher proportion of 1q21 amplification also occurred in the LOY group (10/13 vs 77/162)(χ 2=4.159, P<0.05). The proportion of complete response(CR)/stringent complete response(sCR) in the normal karyotype group after the fourth chemotherapy (63/171) was significantly higher than that in the LOY group (1/15)(χ 2=5.564, P<0.05). The proportion of progressive disease (PD) was lower in the normal karyotype group (16/171 vs 4/15) (χ 2=4.306, P<0.05). The 2-year progression-free survival (PFS) of MM patients for the LOY group was significantly shorter compared to that for the normal karyotype group ( Z=?3.201, P<0.01). Univariate survival analysis showed that PFS was significantly shorter in newly diagnosed MM patients with Creatinine(Cr)≥93 μmol/L, β 2-microglobulin (β 2-MG)≥4.0 mg/L, serum free light chain(sFLC)<0.06, bone marrow plasma cells (BMPC)≥30%, R-ISS stage Ⅲ, failure to achieve CR/sCR after the fourth chemotherapy, with LOY, 1q21 amplification, P53 deletion and t(4;14) ( P<0.05). Cox regression analysis showed that Cr≥93 μmol/L( HR=4.460, 95% CI 1.615-12.314, P=0.004), sFLC<0.06( HR=2.873, 95% CI 1.206-6.849, P=0.017), failure to achieve CR/sCR after the fourth chemotherapy( HR=3.522, 95% CI 1.437-8.634, P=0.006)and with LOY( HR=3.485, 95% CI 1.473-8.249, P=0.006)were independent risk factors for PFS in newly diagnosed MM patients. Conclusions:LOY is an independent risk factor for poor prognosis. It is important for the clinical outcome and prognosis of patients with newly diagnosed MM, and may become a novel clinical assessment indicator.

Openness and innovation are the key driving forces for promoting laboratory medicine to higher level / 中华检验医学杂志

The rapid development of laboratory medicine contributes greatly to the constant improvement on the quality of research papers published in the Chinese Journal of Laboratory Medicine. Compared with the status of international laboratory medicine and the level of international journals of laboratory medicine, there are still plant of rooms for improvement for the Chinese Journal of Laboratory Medicine, and arduous efforts are needed to further improve the quality of research papers published in the Chinese Journal of Laboratory Medicine.

Application of delta checks in clinical laboratories / 中华检验医学杂志

The delta checks are one of the patient-based quality control options to identify the errors and the significant changes in patients′ condition. Compared with the traditional internal quality control method, the delta checks have the characteristics of real-time monitoring, with no additional detecting cost, thus the delta checks are widely used in clinical laboratories. In addition, the delta checks are also useful in the auto-verification system to screen out the abnormal results for manual verification. This article reviewed the delta checks′ development history, parameters selection, application values in quality control and auto-verification.

Advances in the antibody detection and immunotherapy of neutralizing antibodies for 2019-nCoV / 中华检验医学杂志

A novel coronavirus (COVID-19) that broke out in December 2019 has been declared a public health emergency of international concern. Nucleic acid detection has an irreplaceable role in the diagnosis of 2019-novel coronavirus (2019-nCoV) infection. However, due to the high requirements of laboratories and technicians, cumbersome operations, and the possibility of omission, nucleic acid detection should be combined with specific antibodies to achieve large-scale screening of suspected patients and close contacts. Moreover, antibody detection can reduce the exposure risk of medical personnel during the collection of respiratory tract samples.

Cost accounting for diagnosis items based on virtual standardized clinical chemistry laboratory / 中华医院管理杂志

Objective:Cost accounting for its diagnosis items based on virtual standardized clinical chemistry laboratory.Methods:Relevant data of clinical chemistry laboratories from January to June 2019 were extracted from the laboratory information systems of 10 hospitals in Shanghai, and three health economic experts and the directors of their laboratory departments were interviewed in this regard.On such basis, a virtual standardized clinical chemistry laboratory was constructed. The project cost of the virtual laboratory was calculated from the aspects of supplies exhaust, labor and others. The routine clinical chemistry diagnosis items were clustered according to the principle of laboratory methods, and the cost differences of items in the same cluster were compared using paired t test. Results:The cost of rate method and dry chemical method in testing alanine aminotransferase was 5.12 and 11.63 respectively, and that of immune turbidimetry and immune scattering turbidimetry method in testing immunoglobulin G was 20.00 and 22.26 respectively. Cluster analysis was conducted on 214 routine clinical biochemical diagnostic items, of which 202 items were classified into 42 clusters. The average of clinical chemistry items accounted for 91.7%(4 493/4 900)of the total per day. Based on enzymology, the calculation costs of alanine aminotransferase(rate method), aspartate aminotransferase(rate method), cholesterol(enzyme method)and uric acid(enzyme method)was 5.12, 5.10, 5.24 and 5.14 respectively, presenting no statistical difference( P>0.05). Conclusions:Research on the cost accounting method of clinical chemistry laboratory diagnosis items constructed includes labor cost, reflects the technical labor value of medical staff. Cost accounting based on project clustering can provide references for medical service pricing and financial management of hospitals.

The expression differences and prognostic value of four cancer stem cell markers in hepatocellular carcinoma tissues and circulating tumor cells in peripheral blood / 中华检验医学杂志

Objective:To investigate the expression of four cancer stem cell (CSC) markers (EpCAM, CD133, CD90 and CD24) in hepatocellular carcinoma tissues and peripheral blood circulating tumor cells (CTC),their value in the prognosis of patients with hepatocellular carcinoma.Methods:A total of 50 hepatocellular carcinoma tissues and 29 peripheral blood sample from 50 patients with hepatocellular cancer treated in Zhongshan Hospital Fudan University from October 2013 to September 2014 were collected and analyzed by flow cytometry or qRT-PCR to examine the expression of EpCAM, CD133, CD90 and CD24. The clinical data of patients were collected, including tumor size, tumor number, satellite lesions, vascular invasion, Edmondson stage, BCLC stage and liver cirrhosis, etc. The correlation between the expression of four markers in hepatocellular carcinoma tissues and CTC with the clinical data and survival time of patients were compared.Results:The positive expression rates of EpCAM, CD133, CD90 and CD24 in hepatocellular carcinoma tissues were 66% (33/50), 18% (9/50), 60% (30/50) and 56% (28/50); the positive expression rates in CTC were 55% (16/29), 38% (11/29), 31% (9/29) and 59% (17/29). CD90 expression in hepatocellular carcinoma tissue was positively correlated with the occurrence HCC liver cirrhosis ( P<0.05), while CD133 expression was negatively correlated with the 5-year survival rate of patients ( P<0.05). The expression of EpCAM and CD24 in peripheral blood CTC were closely related to the patient′s Edmondson stage ( P<0.05). The survival time of patients with CD133 positive expression in hepatocellular carcinoma tissue was lower than those without CD133 expression ( P<0.05); the survival rate of patients with EpCAM expressed in either tissue or peripheral blood CTC was lower than that of patients with EpCAM double negative expression ( P<0.05). The survival rate of patients with CD90 negative in HCC tissue and positive in peripheral blood was lower than that in patients with double negative/double positive in tissue and peripheral blood or patients positive in hepatocellular carcinoma tissue and negative in peripheral blood ( P<0.01). Conclusion:Different expression characteristics of four markers in cancer tissues and peripheral blood CTC might provide useful information about predicting prognosis of hepatocellular carcinoma. The expression of CD133 in tissues can be used as an important survival predictor of hepatocellular carcinoma patients. The differential expression of cancer markers in tissue samples and blood samples can provide more clinical prognostic information.

Theories and perspectives of patient-based real-time quality control system in the laboratory / 中华检验医学杂志

Taking advantage of current advancements of the laboratory information system, patient-based real-time quality control (PBRTQC) has become a hot research topic with the potential of significantly improving the quality of clinical laboratories. PBRTQC has several advantages over conventional internal quality control, including the merit of continuous error detection, low maintenance cost, and no fear of loss of quality control due to commutability issue. This review summarized the recent research progress in PBRTQC. The review described the fundamental theories of PBRTQC and explained how to implement PBRTQC in clinical laboratories in detail. The review also provided prospective view on how to solve the current problems and what are the future research directions of PBRTQC.

Evaluation of different platform detection of cfDNA tumor mutation in patients with NSCLC / 中华检验医学杂志

Objective:To verify the performance of the next-generation sequencing (NGS) platform and evaluate the application of NGS, droplet digital PCR (ddPCR) and super amplification refractory mutation system (super-ARMS) in the detection of circulating free DNA (cfDNA) mutations in patients with non-small-cell lung cancer (NSCLC).Methods:A total of 75 patients with NSCLC in the respiratory department of Zhongshan Hospital Affiliated to Fudan University were enrolled. The standards, cfDNA from 25 patients with newly diagnosed and untreated NSCLC, and self-made mixed samples mixed with hemoglobin (1 000 mg /dl), bilirubin (500 mg/l), fat emulsion (2%), enterococcus gDNA and Escherichia coli gDNA were used to verify the blank limit, analytical sensitivity, precision, accuracy and specificity of NGS platform. The cfDNA mutations of 75 NSCLC patients were detected by ddPCR and NGS, and the mutation positive rates of the two platforms were compared. The linear relationship between the two platforms was compared by Pearson correlation test. 12 patients were selected by simple random sampling for the detection of plasma super-ARMS platform. The performance of three platforms in the detection of plasma cfDNA mutation in patients with NSCLC was compared.Results:The blank limit of NGS platform was set to 0.00%, the analytical sensitivity was 0.2%, the intra-assay precision and inter-assay precision were 100%. The test results were not affected by endogenous hemoglobin, bilirubin or fat emulsion in plasma or exogenous DNA interference, and the analysis specificity was good. The mutation positive rates of plasma cfDNA in 75 NSCLC patients detected by ddPCR and NGS were 61.33% and 60.00%, respectively. The complete coincidence rate was 89.33%, which suggests there was a positive correlation between the mutation abundance of NGS and ddPCR ( r=0.984, P=0.001). Among the plasma of 12 NSCLC patients, the results of NGS, ddPCR and super-ARMS were completely consistent in 7 cases, including 2 wild-types and 5 mutants. Conclusion:The NGS platform was verified to be useful for cfDNA mutation detection in patients with NSCLC. The ddPCR, NGS and super-ARMS have their own advantages in detecting cfDNA mutations in patients with NSCLC.

Improving clinical outcomes through advances in point-of-care testing / 中华检验医学杂志

Point-of-care testing (POCT) systems has been widely used in clinical practice. It is necessary to carefully review and summarize issues related to the testing speed, cost, and quality of POCT. Guidelines and standardization documents for clinical application of POCT need to be formulated as soon as possible. These works would contribute to the accuracy and reliability of POCT results and help the accurate application of POCT in clinical practice.

Value of advanced clinical lipids research and measurements / 中华检验医学杂志

Dyslipidemias played the critical role in cardiovascular disease risk assessment. Evaluate the benefits and limitations of advanced clinical lipids research and measurements would be important for assessing and managing cardiovascular risk.

Construction of laboratory medicine suitable for large-scale public health events / 中华检验医学杂志

The medical laboratories have played the important role in fighting against the pandemic of COVID-19. It′s critical to improve response strategy and better prepare to create robust and sustainable medical laboratories for future outbreaks of public health events. The general framework to guide the construction of the qualified medical laboratories is discussed.

Review of Shanghai glycohemoglobin harmonization program / 中华检验医学杂志

Objective:To review the results of inter-laboratory comparisons in Shanghai glycohemoglobin harmonization program from 2010 to 2018, and to analyze the evolution of quality levels of HbA 1c determination, so as to provide the reference for improving the HbA 1c determination quality in China. Methods:Retrospective analysis. The comparison data of Shanghai Glycohemoglobin Harmonization Program from 2010 to 2018 was collected. And the change trend was analyzed about hospital and determination method distribution. The judgment criteria, quarterly and annual pass rate, bias and coefficient of variation of the results of the inter-laboratory comparison were analyzed retrospectively, and the results were compared with the results of External Quality Assessment Programme carried out by the National Center for Clinical Laboratories, Shanghai Center for Clinical Laboratories and College of American Pathologists (CAP). The data in the first quarter of 2019 was collected and the imprecision, bias and sigma were calculated, which were drew in the evaluation model of sigma combined with biomedical variation parameters.Results:The number of participating laboratories increased from 9 in Shanghai to 192 in the whole country, with an average annual growth rate of 76.6%. The quarterly comparison criteria improved from ±8% to ±6% and the passing rate of participating laboratories increased from 39.1% to nearly 90%. The maximum CV of each instrument among laboratories decreased from 14.3% to 4.8%. In the first quarter of 2019, nearly 60% of the laboratories met 6σcriteria and more than 95% of the laboratories met the "standard criteria" in the model of biological variation parameters.Conclusion:Shanghai Glycohemoglobin harmonization program has improved the harmonization of HbA 1c test results among the participating laboratories.

Review of Shanghai glycohemoglobin harmonization program / 中华检验医学杂志

Objective@#To review the results of inter-laboratory comparisons in Shanghai glycohemoglobin harmonization program from 2010 to 2018, and to analyze the evolution of quality levels of HbA1c determination, so as to provide the reference for improving the HbA1c determination quality in China.@*Methods@#Retrospective analysis. The comparison data of Shanghai Glycohemoglobin Harmonization Program from 2010 to 2018 was collected. And the change trend was analyzed about hospital and determination method distribution. The judgment criteria, quarterly and annual pass rate, bias and coefficient of variation of the results of the inter-laboratory comparison were analyzed retrospectively, and the results were compared with the results of External Quality Assessment Programme carried out by the National Center for Clinical Laboratories, Shanghai Center for Clinical Laboratories and College of American Pathologists (CAP). The data in the first quarter of 2019 was collected and the imprecision, bias and sigma were calculated, which were drew in the evaluation model of sigma combined with biomedical variation parameters.@*Results@#The number of participating laboratories increased from 9 in Shanghai to 192 in the whole country, with an average annual growth rate of 76.6%. The quarterly comparison criteria improved from ±8% to ±6% and the passing rate of participating laboratories increased from 39.1% to nearly 90%. The maximum CV of each instrument among laboratories decreased from 14.3% to 4.8%. In the first quarter of 2019, nearly 60% of the laboratories met 6σcriteria and more than 95% of the laboratories met the "standard criteria" in the model of biological variation parameters.@*Conclusion@#Shanghai Glycohemoglobin harmonization program has improved the harmonization of HbA1c test results among the participating laboratories.

Performance evaluation of methylation detection of plasma Septin[STHZ]9[STBZ] gene and its diagnostic value in patients with colorectal cancer / 临床检验杂志

Objective@#To evaluate the value of methylation detection of plasma Septin9 gene in the diagnosis of colorectal cancer (CRC) and verify its performance. @*Methods@#The plasma samples from 32 CRC patients before colonoscopy and 10 healthy controls during October 2016 and May 2017 were collected, and the methylation levels of Septin9 gene in these samples were detected by the detection kit of plasma Septin9 gene methylation. The coincidence rate, detection limit and precision of the kit in the diagnosis of CRC were evaluated, and its diagnostic value was compared with that of carcinoembryonic antigen (CEA) and facal immunochemical tests (FIT). @*Results@#The positive and negative coincidence rates of the plasma Septin9 gene methylation kit in the detection of CRC were 100%. The reference materials assigned the detection limit were positive, and the coefficient of variation (CV) of precision was less than 5%, which met the basic performance requirements. The sensitivity, specificity, positive predictive value and negative predictive value of the kit in the diagnosis of CRC were 62.50%, 90.00%, 95.20% and 42.90%, respectively. The detection rate of CRC by the kit was 62.50%, significantly higher than those of FIT (28.13%) and CEA (28.13%) (all P＜0.05). The area under the ROC curve (AUC ROC ) of the kit in the diagnosis of CRC was 0.762, and the detection rate of stage Ⅰ CRC by the kit was 50.00%. @*Conclusion@#The performance of the plasma Septin9 gene methylation kit meets the anticipated clinical requirements, which may be used as a serological marker for the assistant diagnosis of CRC.

Development and prospect of laboratory medicine / 中华检验医学杂志

After more than half a century and several generations' efforts, the clinical laboratories in China have developed rapidly from the "workshop-style" pure manual operation and limited number of assays to the automated, intelligent modern laboratory. In addition to the great development of working condition, environment and equipment, the number of professional staffs, their educational background and technical ability have also been greatly improved. These have doubled the varieties, throughput and decreased turnaround time of testing assays in order to meet the clinical requests. At the same time, the concept of laboratory medicine has changed from "focusing on specimen" to "focusing on patients and clinical needs". The scientific ethics and practical experience of laboratory management and quality control have also been enriched, which provide more reliable and convenient services for patients and clinicians. Nowadays, the rapid development of detection technology, as well as artificial intelligence, network communication and big data which based on computer science, have brought enormousopportunities and challenges to the development of laboratory medicine.

The medical laboratory issues about recommendation on uniform cutoff values of "Normal" ALT in the ACG guidelines / 中华肝脏病杂志

In the recent clinical guidelines dealing with laboratory tests for liver disease evaluation, the American College of Gastroenterology (ACG) recommends ALT upper reference limits of 33 U/L for males and 25 U/L for females, and individuals with results above these "normal" cutoffs should be further investigated. Considering the differences between laboratory assays measuring ALT in our country, the uniform ACG "normal" range may not be suitable for Chinese population. On the other hand, reference upper/lower limits should not be equated with clinical decision thresholds. Simply acting in accordance with the reference range from ACG guidelines for ALT may lead to overdiagnosis and unnecessary follow-up examinations.

The medical laboratory issues about recommendation on uniform cutoff values of "normal" ALT in the ACG guidelines / 临床肝胆病杂志

In the recent American clinical guidelines dealing with laboratory tests for evaluation of liver disease, the American College of Gastroenterology (ACG) recommends ALT upper reference limits of 33 U/L for males and 25 U/L for females respectively, and that individuals with ALT above these"normal"cutoffs should be further investigated. Considering the differences between laboratory assays measuring ALT in our country, the standardization of methods and the consistency of results can not be completely ensured. The uniform "normal"range of ALT recommended by the ACG guidelines is largely based on findings from foreign studies and may not be suitable to Chinese population. On the other hand, reference upper/lower limits should not simply be equated with clinical decision thresholds. However, due to improper application of the related concepts of the above medical laboratory issues, simply recommending the uniform reference range of the ALT may lead to overdiagnosis and unnecessary follow-up examinations.