OBJECTIVE: To investigate the serum level of lumican (LUM) and its clinical correlation with disease and immune activities in patients with rheumatoid arthritis (RA). METHODS: The serum LUM levels in both RA patients and health controls (HCs) were detected by enzyme-linked immunosorbent assay (ELISA). The clinical and laboratory data of the patients were collected. The LUM levels in the patients with different clinical features were analyzed. The correlation between the clinical data, laboratory parameters, and serum LUM levels were also analyzed. Independent samples t test, Spearman correlation were used for statistical analysis. Analysis of variance and Kruskal-Wallis test, the least significant difference (LSD)-t test and Bonferroni correction were used for statistical analysis. The Pearson Chi-square test was used for comparison of the rates between the groups. Statistical significance was set at P < 0.05. RESULTS: The levels of LUM were elevated in the RA patients than in the HCs (P < 0.000 1). Serum LUM levels were correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin A (IgA), titers of platelet (PLT) and 28-joint disease activity score (DAS28, all P < 0.05). Next, we compared the serum LUM levels in the RA patients with different characteristics, and no difference was found in serum LUM levels between early-RA and RA, the same to RA with different gender (P>0.05). The levels of serum LUM were elevated in the RF positive patients (P < 0.000 1), and in the RF and anti-CCP positive patients (P < 0.05) than in the RA patients with negative RF whether the anti-CCP was positive. In addition, no differences were found between the RA patients with negative RF whether the anti-CCP was positive (P>0.05). All the levels of serum LUM were elevated in the RA patients with different CRP or ESR than in the HCs (P < 0.05), and the serum LUM levels in the RA patients with elevated ESR and CRP were significantly elevated in those with normal ESR and CRP (P < 0.05). Additionally, the results demonstrated that serum LUM levels were positively associated with RA disease activity, and they were declined in RA sustained remission than those in middle or high disease activity (P < 0.05). Furthermore, no difference was found between the RA patients in remission and HCs (P>0.05). No differences were found in the RA patients with and without complications including interstitial pneumonia disease, Sjögren's syndrome, thyroid gland diseases and osteoporosis (P>0.05). The LUM positivity rates were significantly elevated in the RF positive patients than the RF negative patients in RA (P < 0.05). CONCLUSION LUM, a cyclocitrullinated protein, might be a promising biomarker which could reflect both disease activity and immune activity in RA.
Humans ; Arthritis, Rheumatoid/immunology* ; Lumican/blood* ; C-Reactive Protein/metabolism* ; Female ; Male ; Rheumatoid Factor/blood* ; Middle Aged ; Adult ; Chondroitin Sulfate Proteoglycans/blood* ; Blood Sedimentation ; Keratan Sulfate/blood* ; Enzyme-Linked Immunosorbent Assay ; Aged

Objective:To explore the clinical phenotype and genotype of a family with hereditary hypofibrinogenemia.Methods:Activated partial thrombin time (APTT), prothrombin time (PT),thrombin time (TT) and thrombelastogram (TEG) were tested in all family members. Fibrinogen activity and antigen were detected by Clauss method and immunoturbidimetric method respectively. All exons and flanking sequences of fibrinogen FGA,FGB,FGG genes were analyzed by PCR, and the products were subjected to Sanger sequencing.Results:The proband represented prolonged PT and TT, low Fg activity and antigen, elevated K value and decreased Angle value in TEG. Other family members reported similar changes including proband′s father,daughter and son, and his elder brother and his niece. Exon 5 c.510_512 of FGG gene in the proband revealed a minor deletion mutation.Conclusion:The novel heterozygous missense mutation of exon 5 c.510_512del (Gln170_Ile171 del ins His) of FGG gene is the molecular mechanism that leads to hereditary hypofibrinogenemia in this family.

Objective: To compare the indirect immunofluorescence staining effect of urinary podocytes by thinprep liquid-based cytologic test (TCT) with that by the conventional centrifugal smear method, and explore its clinical application value. Methods: The morning urine samples from 50 patients with type 2 diabetic nephropathy and 14 healthy controls were smeared with the TCT and conventional centrifugation method, respectively, and then the indirect immunofluorescence staining were performed to observe the morphology of podocytes. Results: For 64 urine samples, the satisfactory rate of TCT smears (85.94%) was significantly higher than that of conventional smears (50.00%), and the podocyte detection rate of TCT smears (73.47%) was also significantly higher than that of conventional smears (51.02%) (P＜0.05). When urinary podocytes of the same patient were positive by both methods, the reading effect of TCT smears was obviously superior to that of conventional smears. Conclusion The TCT combined with indirect immunofluorescence staining is obviously superior to the conventional centrifugal smear method in the podocyte diagnosis of urine samples.

Objective:To investigate the tumor-specific neoantigen for primary plasma cell leukemia (PCL) using gene sequencing technology combined with bioinformatic analysis. Methods: Peripheral blood samples of one patient with primary PCL during relapse and remission periods were collected. HLA molecular typing was performed using polymerase chain reaction with sequencing-based typing; whole-exome and transcriptome were sequenced by next-generation sequencing method; and bioinformatics software NetMHCpan was used to predict neoantigens. Results: Six tumor-specific missense mutations were found in the patient's peripheral blood during relapse period, located in genes FRG1, MLL3, SVIL, MYOM1, ZDHHC11 and RFPL4A.Considering patient's HLA sub-types, 43 neoantigens were predicted via bioinformatics. Considering that FRG1 and MLL3 had relatively high gene expression levels, 20 neoantigens derived from mutations of the two genes were preferentially selected, among which four neoantigens had high affinity with the patient's HLA molecules and thus had potential clinical application value. Conclusion: The study has completed a tumor neoantigen screen and prediction for primary PCL. This practice demonstrates that predicting neoantigen based on tumor-specific somatic mutation is feasible for primary PCL.

Direct oral anticoagulants,include direct thrombin inhibitor and direct factor Xa inhibitor.As the pharmacokinetics and pharmacodynamics of these drugs are known,their plasma concentration is not food-effective,and theoretically it is not necessary to monitor routinely.However, clinical practice in recent years has shown that anticoagulant effect of DOACs is required to evaluate in patients with thrombosis, major bleeding, emergency surgery, hepatic/renal dysfunction and other special situations.Recent studies have shown that routine coagulation assays such as activated partial thromboplastin time(APTT) and thrombin time(TT) can be used as laboratory screening tests for direct thrombin inhibitor dabigatran and prothrombin time(PT) can be used as laboratory screening test for direct factor Xa inhibitor rivaroxaban.DOAC′s quantitative measurements include dilute thrombin time(dTT),hemoclot thrombin inhibitor (HTI),ecarin clotting time (ECT) and ecarin chromogenic assay (ECA) for direct thrombin inhibitor and anti-FXa assay(rivaroxaban calibration) for rivaroxaban.Laboratories should establish their own monitoring range when performing these assays.

Manual microscopic differential of white blood cell has been challenged by multiparameter flow cytometry,using monoclonal antibodies to define the different leukocyte types.Compared with manual differential,flow cytometry method is more sensitive,specific,objective and has good repeatability.Recent studies demonstrated flow cytometric differential correlates well with manual microscopic method and has good clinical performance for blast and immature granulocyte.Meanwhile more leukocyte populations can be identified with flow cytometric method,such as lymphocyte subset and CD 16 + monocyte,thus helping in monitoring blast in acute leukemia,B lymphocyte proliferative disorder differential diagnosis and minimal residual disease.With the development and improvement of flow cytometric differential,it might be a candidate reference method of leukocyte differential,gradually applied in the routine work.