Elevated serum soluble CD27 levels are associated with both disease activity and humoral immune activity in patients with rheumatoid arthritis.

OBJECTIVES: To investigate the serum level of soluble CD27 (sCD27) and its potential clinical significance in rheumatoid arthritis (RA). METHODS: Serum sCD27 levels in RA patients, idiopathic inflammatory myopathy (IIM) patients, systemic lupus erythematosus (SLE) patients and healthy controls (HCs) were detected by enzyme-linked immunosorbent assay. The medical information and laboratory data of the patients were collected. Serum sCD27 levels in RA patients with different clinical features were analysed, as was the correlation between the clinical data and serum sCD27 levels. Independent samples t test, the Mann-Whitney U-test or Wilcoxon signed-rank test, and Spearman correlation were used for statistical analysis. RESULTS: Levels of sCD27 were elevated in RA patients (3898 [2525, 5834] pg/mL) compared with IIM patients (2467 [1939, 3324] pg/mL) or HCs (1659 ± 648 pg/mL) (p 0.001). In addition, serum sCD27 levels correlated with age, erythrocyte sedimentation rate, C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin A, immunoglobulin G, complement 4 and disease activity score in 28 joints in RA patients. Levels of sCD27 were higher in RF-positive RA patients (6054 ± 5842 pg/mL) than in RF-negative patients (3902 ± 2098 pg/mL), and a similar finding was also observed in anti-cyclic citrullinated peptide (anti-CCP) antibody-positive (5810 ± 5671 pg/mL) and anti-CCP-negative (4183 ± 2187 pg/mL) RA patients. Serum ESR, RF, IgA, IgG levels and DAS28-CRP were elevated in RA patients with higher sCD27 levels than in those with lower sCD27 levels (p<0.01). CONCLUSIONS: Serum sCD27 might be a promising biomarker that reflects both disease activity and humoral immunity activity in RA.

Integration of clinical demographics and routine laboratory analysis parameters for early prediction of gestational diabetes mellitus in the Chinese population.

Gestational diabetes mellitus (GDM) is one of the most common complications in pregnancy, impairing both maternal and fetal health in short and long term. As early interventions are considered desirable to prevent GDM, this study aims to develop a simple-to-use nomogram based on multiple common risk factors from electronic medical health records (EMHRs). A total of 924 pregnant women whose EMHRs were available at Peking University International Hospital from January 2022 to October 2022 were included. Clinical demographics and routine laboratory analysis parameters at 8-12 weeks of gestation were collected. A novel nomogram was established based on the outcomes of multivariate logistic regression. The nomogram demonstrated powerful discrimination (the area under the receiver operating characteristic curve = 0.7542), acceptable agreement (Hosmer-Lemeshow test, P = 0.3214) and favorable clinical utility. The C-statistics of 10-Fold cross validation, Leave one out cross validation and Bootstrap were 0.7411, 0.7357 and 0.7318, respectively, indicating the stability of the nomogram. A novel nomogram based on easily-accessible parameters was developed to predict GDM in early pregnancy, which may provide a paradigm for repurposing clinical data and benefit the clinical management of GDM. There is a need for prospective multi-center studies to validate the nomogram before employing the nomogram in real-world clinical practice.

Artificial intelligence of digital morphology analyzers improves the efficiency of manual leukocyte differentiation of peripheral blood.

BACKGROUND AND OBJECTIVE: Morphological identification of peripheral leukocytes is a complex and time-consuming task, having especially high requirements for personnel expertise. This study is to investigate the role of artificial intelligence (AI) in assisting the manual leukocyte differentiation of peripheral blood. METHODS: A total of 102 blood samples that triggered the review rules of hematology analyzers were enrolled. The peripheral blood smears were prepared and analyzed by Mindray MC-100i digital morphology analyzers. Two hundreds leukocytes were located and their cell images were collected. Two senior technologists labeled all cells to form standard answers. Afterward, the digital morphology analyzer unitized AI to pre-classify all cells. Ten junior and intermediate technologists were selected to review the cells with the AI pre-classification, yielding the AI-assisted classifications. Then the cell images were shuffled and re-classified without AI. The accuracy, sensitivity and specificity of the leukocyte differentiation with or without AI assistance were analyzed and compared. The time required for classification by each person was recorded. RESULTS: For junior technologists, the accuracy of normal and abnormal leukocyte differentiation increased by 4.79% and 15.16% with the assistance of AI. And for intermediate technologists, the accuracy increased by 7.40% and 14.54% for normal and abnormal leukocyte differentiation, respectively. The sensitivity and specificity also significantly increased with the help of AI. In addition, the average time for each individual to classify each blood smear was shortened by 215 s with AI. CONCLUSION: AI can assist laboratory technologists in the morphological differentiation of leukocytes. In particular, it can improve the sensitivity of abnormal leukocyte differentiation and lower the risk of missing detection of abnormal WBCs.

Study on Adsorption Characteristics of Deep Coking Coal Based on Molecular Simulation and Experiments.

To study the effect of high temperature and high pressure on the adsorption characteristics of coking coal, Liulin coking coal and Pingdingshan coking coal were selected as the research objects, and isotherm adsorption curves at different temperatures and pressures were obtained by combining isotherm adsorption experiments and molecular dynamics methods. The effect of high temperature and high pressure on the adsorption characteristics of coking coal was analyzed, and an isothermal adsorption model suitable for high-temperature and high-pressure conditions was studied. The results show that the adsorption characteristics of deep coking coal can be well characterized by the molecular dynamics method. Under a supercritical condition, the excess adsorption capacity of methane decreases with the increase of temperature. With the increase of pressure, the excess adsorption capacity rapidly increases in the early stage, temporarily stabilizes in the middle stage, and decreases in the later stage. Based on the classical adsorption model, the adsorption capacity of coking coal under high-temperature and high-pressure environments is fitted. The fitting degree ranges from good to poor. The order is D-R > D-A > L-F >BET > Langmuir, and combined with temperature gradient, pressure gradient, and the D-R adsorption model, it can be seen that after 800 m deep in Liulin Mine and 400 m deep in Pingdingshan Mine, the adsorption capacity of coking coal to methane decreases with the increase of depth.

[Pedigree Analysis of ACTN1-Related Thrombocytopenia Attributed to A Novel Mutation].

AbstractObjective: To investigate the clinical phenotype and genotype of an ACTN1-associated thrombocytopenic family and explore its molecular pathogenesis. METHODS: All the family members' peripheral blood was collected for routine blood tests, blood smear, coagulation function, and platelet aggregation test. Flow cytometry was used to detect the expression of platelet CD41 and CD61. The proband and her father were tested bone marrow cytomorphology. Whole-exome sequencing techniques were performed to detect and uncover mutant loci of suspected pathogenic genes. Bioinformatics was used to assess the conserved nature of the mutated loci and to analyze the effect of the mutated genes leading to the function of the corresponding amino acid sequences. RESULTS: The platelet count of the proband was 88×109/L, and the blood smear showed dumbbell-shaped platelets, snake-shaped platelets and platelets of various sizes. Her bone marrow cytomorphology revealed normal megakaryocyte morphology with a count of 270. The platelet count of the proband's father was 74×109/L, with large platelets and platelets of various sizes observed in the blood smear, and the morphology of megakaryocytes was normal in bone marrow with a megakaryocyte count of 239. Her grandfather had a platelet count of 83×109/L, with snake-shaped platelets and platelets of various sizes on blood smears. Other family members were normal in all tests. The missense mutation c.2396G > A in exon 20 of the ACTN1 gene in the proband resulted in the mutation of 799 amino acids of the encoded protein, i.e., Arg, to His. The sequencing results of her father and grandfather at this locus were found to be consistent with her. Furthermore, bioinformatics analysis indicated that the locus was highly conserved across species and that variation in this locus might lead to functional impairment of the protein. The protein model analysis demonstrated that α-actin-1 at position 799 Arg and Glu at position 811 could form a critical salt bridge which stabilizes the conformation of the Ca2+ binding loop within the calmodulin-like motif. the mutation of R799H lost this critical salt bridge and destabilized this structural domain. CONCLUSION: In the present study, the newly uncovered missense mutation c.2396G＞A in exon 20 of the ACTN1 gene is potentially the molecular mechanism for the thrombocytopenia.

Evaluation of Urine NDRG1 as Noninvasive Biomarker for Bladder Cancer Diagnosis.

BACKGROUND: N-myc downstream regulated gene 1 (NDRG1) was involved in cell differentiation and was recently reported to exert various effects in tumorigenesis. The aim of this study was to assess its diagnostic value in urine as a useful marker for bladder cancer (BC). METHODS: In this study, we recruited 119 BC patients, 65 patients with non-cancerous bladder diseases, and 60 healthy volunteers as control. Their urine concentrations of NDRG1, nuclear matrix protein 22 (NMP22), and creatinine (Cr) were measured and relevant clinical information was retrieved from their medical history records. RESULTS: The expression of NDRG1/Cr and NMP22/Cr in urine were significantly higher in BC patients than those in non-cancerous bladder diseases (p = 0.009 and p = 0.023) and healthy controls (p = 0.005 and p = 0.002). The level of NDRG1/Cr was significantly associated with pathologic T stage (p < 0.001) and pathological grade (p < 0.001). The ROC of NDRG1/Cr to diagnose BC was 0.713 (95% CI, 0.630 - 0.797), with a sensitivity of 63.8% and a specificity of 73.4% at a cutoff of 76.3 ng/mg. NMP22/Cr was 0.705 (95% CI, 0.626 - 0.784), with a sensitivity of 64.2% and a specificity of 66.2% at a cutoff of 12.1 ng/mg. NDRG1/Cr in combination with NMP22/Cr shows a ROC of 0.719 (95% CI, 0.632 0.806) with a sensitivity of 64.9% and specificity of 75.9% Conclusions: Urine NDRG1 may be useful in a minimally invasive modality for determining bladder cancer. Predictive value of the two biomarkers was slightly higher than that of routine NMP22 parameter alone.

Patterns and levels of platelet glycosylation in patients with coronary heart disease and type 2 diabetes mellitus.

Coronary heart disease (CHD) and diabetes mellitus (DM) have high reactivity of platelets and an increased risk of thrombosis. Platelet glycosylation is closely related to platelet function and survival. However, the alteration of platelet glycosylation in CHD and T2DM still remains unknown. Platelet samples were obtained from 55 healthy controls and 102 patients, including 33 CHD, 30 T2DM and 39 CHD complicated with T2DM (CHD + T2DM). Platelet glycosylation was detected using eight-lectin based assay by flow cytometry. Platelet activation markers, such as CD62P (P-Selectin) and activated integrin GPIIb/IIIa (PAC-1), were measured on resting and stimulated conditions by flow cytometry. Platelet aggregation was measured by light transmission aggregometry. In CHD group, platelet surface weakly expressed ß-Gal and 2,6-sialic acid and strongly expressed ß-GlcNAc. In T2DM group, lectins binding to platelet of ß-Gal, 2,6-sialic acid and α-mannose were decreased, while α1,6-fucose and GlcNAc were increased. There was positive correlation between ConA (specific for α-mannose) and PAC-1 in T2DM patients, while negative correlation in healthy controls. Patterns and levels of platelet glycosylation in CHD + T2DM group are a combination of CHD group and T2DM group, in addition to the level of ECL highly elevated (specific for ß-Gal). The level of ConA was significantly correlated with glucose in T2DM group, also correlated with HbA1c in CHD + T2DM. Our findings suggested that platelets decreased in sialylation, galactosylation and mannosylation, and increased in fucosylation and GlcNAcylation in CHD and T2DM patients. The changes of platelet glycosylation may be associated with high platelet reactivity and the increased risk of thrombosis in CHD and T2DM.