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

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.

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.

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.

【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.

Recent research evidence challenges the hypothesis that high density lipoprotein (HDL) has a protective effect on atherosclerosis. Due to the heterogeneity of HDL particle composition and the diversity of HDL functions, the evaluation of HDL particle composition and the detection of HDL function might overcome the deficiency from the measurement of single high-density lipoprotein cholesterol (HDL-C) level. This review briefly introduced the detection method and clinical application for the "quantity" of HDL, and focused on the current status of clinical application and the future development trend of related detection method for the structure and function of HDL. It is postulated that the evaluation of the "quality" of HDL may become the routine method of HDL detection in the future.

Objective: Propionic acidemia is a rare inherited metabolic disorder caused by propionyl CoA carboxylase (PCC) deficiency. This study aims to analyze the clinical characteristics and gene variations of Chinese patients with propionic acidemia, and to explore the correlation between clinical phenotypes and genotypes. Methods: Single-center, retrospective and observational study. Seventy-eight patients of propionic acidemia (46 males and 32 females) from 20 provinces and autonomous regions were admitted from January 2007 to April 2022. Their age of initial diagnosis ranged from 7 days to 15 years. The clinical manifestations, biochemical and metabolic abnormalities, genetic variations, diagnosis, treatment and outcome were studied. Chi-Square test or Mann-Whitney U test were used for statistical analysis. Results: Among 78 cases, 6 (7.7%) were identified by newborn screening; 72 (92.3%) were clinically diagnosed after onset, and the age of onset was 2 hours after birth to 15 years old; 32 cases had early-onset disease and 40 cases had late-onset disease. The initial manifestations included lethargy, hypotonia, vomiting, feeding difficulties, developmental delay, epilepsy, and coma. Among the 74 cases who accepted gene analysis, 35 (47.3%) had PCCA variants and 39 (52.7%) had PCCB variants. A total of 39 PCCA variants and 32 PCCB variants were detected, among which c.2002G>A and c.229C>T in PCCA and c.838dupC and c.1087T>C in PCCB were the most common variants in this cohort. The variants c.1228C>T and c.1283C>T in PCCB may be related to early-onset type. The variants c.838dupC, c.1127G>T and c.1316A>G in PCCB, and c.2002G>A in PCCA may be related to late-onset disease. Six patients detected by newborn screening and treated at asymptomatic stage developed normal. The clinically diagnosed 72 cases had varied complications. 10 (12.8%) cases of them died. 62 patients improved after metabolic therapy by L-carnitine and diet. Six patients received liver transplantation because of recurrent metabolic crisis. Their clinical symptoms were markedly improved. Conclusion: The clinical manifestations of propionic acidemia are complex and lack of specificity. Newborn screening and high-risk screening are keys for early treatment and better outcome. The correlation between the genotype and phenotype of propionic acidemia is unclear, but certain variants may be associated with early-onset or late-onset propionic acidemia.
Carnitine ; Female ; Genotype ; Humans ; Male ; Methylmalonyl-CoA Decarboxylase/metabolism* ; Mutation ; Phenotype ; Propionic Acidemia/genetics* ; Retrospective Studies

Objective:To establish a candidate reference procedure for the enumeration of cell particles in urine and applied to the multi-center performance evaluation of an automated urine formed elements analyzer.Methods:According to the standardized mannual microscopic examination of fresh non-centrifuged urine samples and the recommended reference method for enumeration of cell particles in urine published by ISLH, we established a candidate reference procedure for the enumeration of cell particles in urine. From four class A tertiary hospitals′ clinical laboratories, three rigorous trained technicians per hospital tested the same specimen respectively using the reference procedure. Each specimen was repeatedly counted 5 times, obtaining the quantitative results of cell particles were obtained in urine. Four hospitals used the established candidate reference measurement procedure and the automated urine formed elements analyzer to detect 40 to 60 urine specimens from September 2020 to January 2021, and evaluate the established reference method, meanwhile evaluate the accuracy and consistency of the each count from automated urinalysis analyzer.Results:Using the candidate reference measurement procedures, the coefficient of variation of results derived from three trained technicians per hospital was less than 6.98% (red blood cells), 6.99% (white blood cells), 13.94% (epithelial cells) and met the quality requirements. The performance evaluation results of automated urine formed elements analyzer showed that the accuracy of red blood cells, white blood cells and epithelial cells met the requirements (bias≤4.98%) and was well consistent with the reference measurement procedure ( R2≥0.989). Conclusions:A candidate reference measurement procedure for the enumeration of urine cell particles was successfully established with satisfactory precision and accuracy. This procedure was applied to multicenter performance evaluation of an automated urine formed elements analyzer with good accuracy and consistency.

【Objective】 To study the effect of intravenous immunoglobulin(IVIG) on the detection of blood transfusion compatibility in patients. 【Methods】 56 patients, submitted to our Hospital from March 1, 2017 to December 31, 2020, were enrolled as the research objects. They had negative unexpected antibody screening, major crossmatch incompatibility with the same blood type donors, and had a history of IVIG infusion. ABO and RhD blood groups typing, unexpected antibodies screening, crossmatch, direct antiglobulin test, indirect antiglobulin test, and acid elution test were all conducted by microcolumn gel method. 【Results】 After IVIG infusion, the initially major crossmatch incompatibility with the same blood type donors turned into compatiblity with O-type donors. Among them, 2 patients had transient discrepancy in ABO forward and reverse blood typing due to the IVIG infusion. IgG anti-A were detected in the red blood cell elution of 37 A-type patients; IgG anti-B in 2 B-type patients; 3 cases of IgG anti-A+ anti-B and 14 cases of solo IgG anti-A in 17 AB-type patients. 3 batches of IVIG preparations were detected randomly, IgG anti-A titer was 32-64, and IgG anti-B titer was 8-16. 【Conclusion】 The discrepancy in ABO forward and reverse blood typing and major crossmatch incompatibility with the same blood type donors may occur after non-O type patients received IVIG, which contains IgG types of anti-A and anti-B. In this situation, it is recommended to prepare major crossmatched O-type washed red blood cells to ensure the safety and effectiveness of clinical blood transfusion.

Advanced lipid testing is an extension of traditional standard blood lipid testing. These biomarkers have has been widely used in the risk assessment and differential diagnosis of atherosclerotic cardiovascular disease (ASCVD), especially for people with unclear diagnosis and other metabolic risk factors. However, the differences in the measurement results and traceability issues limit the widespread use of these biomarkers. This article aims to introduce and discuss the current status of clinical application of advanced lipid testing in risk assessment of ASCVD, the progress of detection technology and detection standardization in the field.