1.Comparison and application of direct and indirect methods in establishing reference intervals for coagulation tests
Jing ZHENG ; Ping WANG ; Jiang LI ; Qinmei CAO ; Yongtong CAO
Chinese Journal of Preventive Medicine 2025;59(3):359-364
This study aimed to establish adult reference intervals for coagulation parameters using the CN-6000 fully automated coagulation analyzer. It also compared the applicability of direct and indirect methods in different populations. A cross-sectional and retrospective design was employed. The direct method included patients from the colorectal surgery and dermatology departments, as well as healthy participants from phase I clinical trials, admitted to the West Campus of China-Japan Friendship Hospital from April to December 2023. Participants were divided into two age groups: younger adults (18-64 years) and older adults (≥65 years). Coagulation parameters were tested, and reference intervals were determined. The indirect method applied the refineR algorithm to analyze coagulation data from non-ICU patients during the same period. The performance of both methods was evaluated in healthy participants, relatively healthy patients, and patients with high disease prevalence. The results showed that the direct method yielded similar reference intervals for APTT, PT, and TT in younger and older groups, with combined intervals of 23.7-31.2 seconds, 10.4-12.8 seconds, and 14.7-17.5 seconds, respectively. However, the Fib showed a significant difference between the two groups ( U=1 052 023, P<0.01), and separate reference intervals were established: 1.7-4.5 g/L for the younger group and 2.1-4.6 g/L for the older group. The reference intervals derived by the indirect method are similar to those from the direct method: APTT 23.8-31.4 seconds, PT 10.4-13.0 seconds, TT 14.5-17.4 seconds, and Fib 1.8-4.3 g/L (18-64 years) and 2.1-4.5 g/L (≥65 years). In relatively healthy patients, the reference intervals obtained by both methods were comparable, but significant differences were observed in patients with high disease prevalence. In conclusion, this study established localized reference intervals for the CN-6000 fully automated coagulation analyzer. The indirect method can serve as an alternative to the direct method in healthy and relatively healthy populations. However, its applicability in populations with high disease prevalence is limited and requires cautious interpretation in the context of clinical settings.
2.The correlation between serum calcium binding protein S100A9 and pulmonary function in patients with idiopathic pulmonary fibrosis
Tie ZHANG ; Jing ZHENG ; Guozhen WANG ; Yongtong CAO
Chinese Journal of Laboratory Medicine 2025;48(3):390-395
Objective:To investigate the correlation between serum calcium binding protein S100A9 levels and lung function in patients with idiopathic pulmonary fibrosis (IPF).Method:A retrospective case-control study was conducted. Forty patients diagnosed with IPF in respiratory department from January 4, 2023, to January 30, 2024 were selected as the IPF group,with a mean age of (65.3±8.4) years old, including 29 males and 11 females. while 50 healthy volunteers receiving health examinations in our physical examination center were enrolled in this study, including 38 males and 12 females, with a mean age of (64.1±6.3) years. The levels of biochemical parameters were assayed with biochemical analyzer. S100A9 levels were determined by Enzyme linked immunosorbent assay. The lung function test results of all participants were recorded. SPSS 19.0 statistical software was used to compare the differences of biomarkers levels between the two groups , Using parameter testing (independent sample t-test) to compare the differences in serum S100A9 levels and lung function between the two groups, the enumeration data were treated with the chi-square test. Pearson correlation analysis was used to evaluate the correlation between S100A9 and lung function, the influencing factors of IPF were analyzed by using multivariate logistic regression model, and receiver operating characteristic (ROC) curve analysis was used to assess the value of Calprotectin S100A9 in predicting IPF. Results:The serum S100A9 levels in the IPF group were significantly higher than those in the healthy control group [(132.47±21.46) pg/ml,(44.75±8.84) pg/ml, t=3.544, P<0.05], forced expiratory volume in one second(FEV1,1.38±0.19) L, forced vital capacity (FVC, 2.38±0.59) L, FEV1/FVC (57.98±6.13), the maximum spontaneous ventilation (MVV, 57.48±7.66) L/min was lower than that of the control group [(3.24±0.65) L, (3.65±0.67) L, (88.77±7.97), (86.34±7.23) L/min, t=3.486,3.393,2.771,3.462, P<0.05]. Serum S100A9 was negatively correlated with FEV1, FVC, FEV1/FVC, and MVV ( r=-0.537,-0.458,-0.489,-0.511, P<0.05), S100A9 was positively correlated with S100A9 in bronchoalveolar lavage fluid and high-resolution CT fibrosis score ( r=0.632, r=0.517, P<0.05).The area under the curve (AUC) of S100A9 for predicting IPF was 0.691. Conclusion:The level of calcium binding protein S100A9 was significantly increased in IPF patients, and was closely related to decreased lung ventilation function and the occurrence of IPF, which might serve as a marker for evaluating pulmonary fibrosis.
3.Comparison and application of direct and indirect methods in establishing reference intervals for coagulation tests
Jing ZHENG ; Ping WANG ; Jiang LI ; Qinmei CAO ; Yongtong CAO
Chinese Journal of Preventive Medicine 2025;59(3):359-364
This study aimed to establish adult reference intervals for coagulation parameters using the CN-6000 fully automated coagulation analyzer. It also compared the applicability of direct and indirect methods in different populations. A cross-sectional and retrospective design was employed. The direct method included patients from the colorectal surgery and dermatology departments, as well as healthy participants from phase I clinical trials, admitted to the West Campus of China-Japan Friendship Hospital from April to December 2023. Participants were divided into two age groups: younger adults (18-64 years) and older adults (≥65 years). Coagulation parameters were tested, and reference intervals were determined. The indirect method applied the refineR algorithm to analyze coagulation data from non-ICU patients during the same period. The performance of both methods was evaluated in healthy participants, relatively healthy patients, and patients with high disease prevalence. The results showed that the direct method yielded similar reference intervals for APTT, PT, and TT in younger and older groups, with combined intervals of 23.7-31.2 seconds, 10.4-12.8 seconds, and 14.7-17.5 seconds, respectively. However, the Fib showed a significant difference between the two groups ( U=1 052 023, P<0.01), and separate reference intervals were established: 1.7-4.5 g/L for the younger group and 2.1-4.6 g/L for the older group. The reference intervals derived by the indirect method are similar to those from the direct method: APTT 23.8-31.4 seconds, PT 10.4-13.0 seconds, TT 14.5-17.4 seconds, and Fib 1.8-4.3 g/L (18-64 years) and 2.1-4.5 g/L (≥65 years). In relatively healthy patients, the reference intervals obtained by both methods were comparable, but significant differences were observed in patients with high disease prevalence. In conclusion, this study established localized reference intervals for the CN-6000 fully automated coagulation analyzer. The indirect method can serve as an alternative to the direct method in healthy and relatively healthy populations. However, its applicability in populations with high disease prevalence is limited and requires cautious interpretation in the context of clinical settings.
4.The correlation between serum calcium binding protein S100A9 and pulmonary function in patients with idiopathic pulmonary fibrosis
Tie ZHANG ; Jing ZHENG ; Guozhen WANG ; Yongtong CAO
Chinese Journal of Laboratory Medicine 2025;48(3):390-395
Objective:To investigate the correlation between serum calcium binding protein S100A9 levels and lung function in patients with idiopathic pulmonary fibrosis (IPF).Method:A retrospective case-control study was conducted. Forty patients diagnosed with IPF in respiratory department from January 4, 2023, to January 30, 2024 were selected as the IPF group,with a mean age of (65.3±8.4) years old, including 29 males and 11 females. while 50 healthy volunteers receiving health examinations in our physical examination center were enrolled in this study, including 38 males and 12 females, with a mean age of (64.1±6.3) years. The levels of biochemical parameters were assayed with biochemical analyzer. S100A9 levels were determined by Enzyme linked immunosorbent assay. The lung function test results of all participants were recorded. SPSS 19.0 statistical software was used to compare the differences of biomarkers levels between the two groups , Using parameter testing (independent sample t-test) to compare the differences in serum S100A9 levels and lung function between the two groups, the enumeration data were treated with the chi-square test. Pearson correlation analysis was used to evaluate the correlation between S100A9 and lung function, the influencing factors of IPF were analyzed by using multivariate logistic regression model, and receiver operating characteristic (ROC) curve analysis was used to assess the value of Calprotectin S100A9 in predicting IPF. Results:The serum S100A9 levels in the IPF group were significantly higher than those in the healthy control group [(132.47±21.46) pg/ml,(44.75±8.84) pg/ml, t=3.544, P<0.05], forced expiratory volume in one second(FEV1,1.38±0.19) L, forced vital capacity (FVC, 2.38±0.59) L, FEV1/FVC (57.98±6.13), the maximum spontaneous ventilation (MVV, 57.48±7.66) L/min was lower than that of the control group [(3.24±0.65) L, (3.65±0.67) L, (88.77±7.97), (86.34±7.23) L/min, t=3.486,3.393,2.771,3.462, P<0.05]. Serum S100A9 was negatively correlated with FEV1, FVC, FEV1/FVC, and MVV ( r=-0.537,-0.458,-0.489,-0.511, P<0.05), S100A9 was positively correlated with S100A9 in bronchoalveolar lavage fluid and high-resolution CT fibrosis score ( r=0.632, r=0.517, P<0.05).The area under the curve (AUC) of S100A9 for predicting IPF was 0.691. Conclusion:The level of calcium binding protein S100A9 was significantly increased in IPF patients, and was closely related to decreased lung ventilation function and the occurrence of IPF, which might serve as a marker for evaluating pulmonary fibrosis.
5.Research progress on biomarkers in the diagnosis and treatment of idiopathic pulmonary fibrosis
Lijuan HU ; Ruoyu LIU ; Yun ZHOU ; Yongtong CAO
Chinese Journal of Laboratory Medicine 2024;47(10):1123-1125
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease that is difficult to diagnose clinically, and finding appropriate biomarkers to assist in the diagnosis and prognosis monitoring of IPF can improve the proportion of early diagnosis and timely treatment of these patients and improve the quality of life of patients
6.Application of multi-parameter model based on test indicators in clinical evaluation of idiopathic pulmonary fibrosis
Lijuan HU ; Ruoyu LIU ; Yun ZHOU ; Yongtong CAO
Chinese Journal of Laboratory Medicine 2024;47(10):1139-1151
Objective:The combined diagnosis models was constructed with the test indicators and its application value in the clinical evaluation of patients with interstitial lung disease was evaluated.Methods:Methodology development and validation. A total of 101 patients with idiopathic pulmonary fibrosis (IPF) and 107 patients with non-IPF interstitial lung disease admitted to China-Japan Friendship Hospital from 2022 to 2023 were collected, and 98 healthy people were collected during the same period. The population in each group was divided into modeling group (180 cases) and validation group (126 cases) by complete randomization. Serum samples and clinical test results were collected. The test indicators included white blood cell count, lymphocyte count, monocyte count, hemoglobin concentration, highly sensitive C-reactive protein, Krebs von den Lungen 6, total cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol, adenosine deaminase, neuron-specific enolase, alpha-fetoprotein, carcinoembryonic antigen, cytokeratin 19 fragment, carbohydrate antigen 15-3, gastrin releasing peptide precursor, squamous cell carcinoma antigen and interleukin 1 (IL-1), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, tumor necrosis factor-α, interferon-α, interferon-γ. Multiple collinearity test, univariate and multivariate logistic regression were performed for the included test indicators in each group, and nomograms were established and validated by receiver operating characteristic (ROC) curves, calibration curves and clinical decision curves.Results:By comparing interstitial lung disease to healthy people, carbohydrate antigen 15-3 ( OR=1.285, 95% CI 1.178-1.402), IL-6 ( OR=1.128, 95% CI 1.011-1.258), adenosine deaminase ( OR=1.465, 95% CI 1.261-1.702), and Krebs von den Lungen-6 ( OR=1.013, 95% CI 1.008-1.017) were independent risk factors for interstitial lung disease. Based on these four indexes, the nomogram model was constructed. The AUCs of the combined diagnosis model in the modeling group and validation group were 0.967(95%CI 0.941-0.993)and 0.948(95% CI 0.911-0.984), respectively.Decision curve analysis showed that the net benefit of the combined diagnosis model in diagnosing IPF was higher than that of a single indicator within the threshold range of 0.01-1. In the comparison of IPF and non-IPF interstitial lung disease, alpha-fetoprotein ( OR=1.403, 95% CI 0.975-2.019) and squamous cell carcinoma antigen ( OR=0.531, 95% CI 0.321-0.878) were independent risk factors for IPF. The AUCs of the combined diagnosis model in the modeling group and validation group were 0.703 (95% CI 0.597-0.81) and 0.642 (95% CI 0.528-0.757), respectively. Through calibration curve and clinical decision curve verification, it was found that it had a certain value in the differential diagnosis of IPF. Conclusions:Carbohydrate antigen 15-3, IL-6, adenosine deaminase and Krebs von den Lungen 6 are risk factors of interstitial lung disease, which can be used to construct a combined diagnostic model for the diagnosis of interstitial lung disease. Alpha-fetoprotein and squamous cell carcinoma antigen are risk factors of IPF, which can be used to construct a combined diagnostic model to distinguish IPF from non-IPF interstitial lung disease and assist clinical diagnosis of IPF.
7.The diagnostic value of urine proteomics in interstitial lung disease
Lilong WEI ; Yun ZHOU ; Liwei WANG ; Qingwan SONG ; Zhengguang GUO ; Yongtong CAO
Chinese Journal of Laboratory Medicine 2024;47(10):1159-1168
Objective:To evaluate the diagnostic value of urine proteomics in interstitial lung disease.Methods:A case control study was conducted. 10 patients (age 56.70±14.78 years) with interstitial lung disease, 9 patients (age 51.30±23.26 years) with pulmonary infection and 10 healthy controls (age 50.20±6.07 years) from the physical examination center were selected from China-Japan Friendship Hospital from March 12 to April 15, 2023. The urine proteomics of three groups of people were studied using Liquid chromatography-mass spectrometry proteomics technology. Based on Data-Independent Acquisition mass spectrometry quantitative technology, three groups of people were compared, and t-test was performed between groups and relevant functional analysis was conducted.Results:A total of 2 730 proteins were identified. Three groups of people can be clearly distinguished by urine proteome using partial least squares discriminant analysis based on orthogonal signal correction. Quantitative comparison of proteins was conducted by the screening criteria for differential proteins with P<0.05 and protein abundance fold changes of>3/2 or<2/3. 49 proteins between interstitial lung disease patients and healthy people, as well as 57 proteins between interstitial lung disease patients and infectious diseases patients, were significantly changed. ECM receptor interaction and complement-coagulation cascade pathways were enriched by GO enrichment and KEGG analysis on differentially expressed proteins. Conclusions:Urinary proteomics can effectively distinguish patients with interstitial lung disease from those with pulmonary infections and the normal population. The differential proteins identified in this experiment have certain diagnostic performance (AUC value 0.68-1.00) and can be used as potential disease markers for the diagnosis of interstitial lung disease.
8.Research progress on senescence-associated secretory phenotypes in idiopathic pulmonary fibrosis
Lijuan HU ; Ruoyu LIU ; Yun ZHOU ; Yongtong CAO
Chinese Journal of Laboratory Medicine 2024;47(10):1215-1224
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease that occurs mostly in the middle-aged and eldly people, with a short median survival and cannot be cured, and the etiology is still unclear. Currently, it is believed that the pathogenesis is related to cellular aging, and abnormal cellular aging leads to the failure of damaged alveolar epithelial cells that cannot be repaired normally, which promotes the occurrence of pulmonary fibrosis. Senescence-associated secretory phenotype (SASP), SASP affects pulmonary fibrosis through different signaling pathways in IPF patients, and this article reviews the expression level and mechanism of existing SASP in IPF patients.
9.Risk factors of transfusion-related circulating overload in inpatients and their relationship with clinical outcome
Yu ZHAO ; Mengmeng HAO ; Xixi LIU ; Yongtong CAO
Chinese Journal of Blood Transfusion 2023;36(6):504-507
【Objective】 To investigate the risk factors of transfusion-related circulating overload (TACO) in hospitalized patients and to analyze its impact on clinical outcome. 【Methods】 The clinical data of 295 patients with blood transfusion admitted to our hospital from June 2020 to June 2022 were retrospectively analyzed. The patients were divided into TACO group (n=23) and control group (n=272) according to the incidence of TACO. The risk factors of TACO were analyzed by Logistic regression, and the differences of hospital stay and mortality between the TACO group and the control group were compared. 【Results】 TACO occurred in 23 of 295 patients, accounting for 7.80% of all transfusion reactions. The incidence of TACO in different transfusion components was different. Elder age, history of heart failure, history of chronic kidney disease, large mean blood transfusion volume, positive fluid balance [OR(95%CI)): 2.022 (1.212-3.372), 1.917(1.258-2.922), 1.719 (1.155-2.560), 2.252 (1.256- 4.039), 2.221 (1.358-3.633)] were the main risk factors for TACO (P<0.05). 【Conclusion】 Elder age, history of heart failure, history of chronic kidney disease, large blood transfusion volume and positive fluid balance were risk factors for TACO, and TACO was associated with increased length of stay and mortality during hospitalization.
10.Application of GeneXpert MTB/RIF technology in rifampicin resistance gene mutation of Mycobacterium tuberculosis
LIN Yongtong ; MAI Shikang ; HUANG Long ; LI Yonghua ; WANG Guanyu ; CHEN Licui
China Tropical Medicine 2023;23(7):748-
Abstract: Objective To analyze the accuracy and feasibility of GeneXpert MTB/RIF (GeneXpert) detection in the detection of Mycobacterium tuberculosis and the characteristics of rifampicin-resistant rpoB gene mutations. Methods A total of 4 234 sputum samples from suspected tuberculosis patients diagnosed in Sanya tuberculosis designated hospitals from 2015 to 2021 were selected and subjected to sputum smear, solid culture, drug sensitivity test by solid proportion method and GeneXpert detection. Results The positive detection rates of sputum smear, solid culture and GeneXpert of 4 234 sputum samples were 29.24% (1 238/4 234), 32.17% (1 362/4 234) and 35.40% (1 499/4 234), respectively. The positive detection rate of GeneXpert was higher than that of sputum smear, and the difference was statistically significant (χ2=36.775, P<0.01). It was slightly higher than solid culture, and the difference was not statistically significant (χ2=9.908, P=0.02). Taking solid culture results as the gold standard, the sensitivity and specificity of GeneXpert for detecting MTB were 91.04% (1 240/1 362) and 90.98% (2 613/2 872), respectively. According to the proportional drug susceptibility test results as the gold standard, the sensitivity and specificity of GeneXpert in detecting rifampicin resistance were 96.96% (96/99) and 98.86% (1 128/1 141), respectively, with the consensus rate of 98.71%. The accuracy of rifampicin resistance in GeneXpert group without probe mutation was significantly lower than that in group with probe mutation. There was a statistical difference in probe mutation frequency between newly treated and retreated cases. The analysis of rpoB gene mutation frequency characteristics showed: Probe E (50.00%) > Probe A (22.12%) > Probe D (14.42%) > Probe B (6.73%) > combined probe (5.77%) > Probe C (0.96%). Conclusions GeneXpert detection can quickly and effectively diagnose rifampicin-resistant tuberculosis, which is helpful for early clinical diagnosis and treatment. In this region, the rpoB gene mutation probes of rifampicin-resistant tuberculosis mainly occurr in Probe E and Probe A, with the least mutations in Probe C.

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