Genetic polymorphisms in NOD1 and NOD2 may interact with H. pylori infection and may play important roles in promoting the development of gastric cancer in the Chinese population.

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Background: There is no simple method for early diagnosis and evaluation of rheumatoid arthritis (RA). This study aimed to determine potential biomarkers and establish diagnostic patterns for RA using proteomic fingerprint technology combined with magnetic beads.Methods: The serum protein profiles of 97 RA patients and 76 healthy controls (HCs) were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) with weak cationic exchange (WCX) magnetic beads. Samples were randomly divided into training (83 RA patients and 56 HCs) and test sets (14 RA patients and 20 HCs). Patients were classified according to their Disease Activity Score: in remission, n = 28; with low disease activity, n = 17; with moderate disease activity, n = 21; with high disease activity, n = 31. There are 44 RA patients alone, 22 RA patients with interstitial lung disease (RA-ILD), 18 RA patients with secondary Sjögren's syndrome (RA-sSS), 6 RA patients with osteonecrosis of the femoral head (RA-ONFH), and 7 RA patients with other complications. Eleven patients were treated with etanercept only for half a year, after which their serum protein profiles were detected. The proteomic pattern was identified by Biomarker Patterns Software, and the potential biomarkers for RA diagnosis were further identified and quantified by enzyme-linked immunosorbent assay.Results: The diagnostic pattern with four potential protein biomarkers, mass-to-charge (m/z) 3,448.85, 4,716.71, 8,214.29, and 10,645.10, could accurately recognize RA patients from HCs (specificity, 91.57%; sensitivity, 92.86%). The test set were correctly classified by this model (sensitivity, 95%; specificity, 100%). The components containing the four biomarkers were preliminarily retrieved through the ExPasy database, including the C-C motif chemokine 24 (CCL24), putative metallothionein (MT1DP), sarcolipin (SLN), and C-X-C motif chemokine 11 (CCXL11). Only the CCL24 level was detected to have a significant decrease in the serum of RA patients as compared with HCs (p < 0.05). No significant difference was found in others, but a decreasing trend consistent with the down-regulation of the four biomarkers detected by MALDI-TOF-MS was observed. The diagnostic models could effectively discriminate between RA alone and RA with complications (RA-ILD: m/z 10,645.10 and 12,595.86; RA-sSS: m/z 6,635.62 and 33,897.72; RA-ONFH: m/z 2,071.689). The classification model, including m/z 1,130.776, 1,501.065, 2,091.198, and 11,381.87, could distinguish between RA patients with disease activity and those in remission. RA with low disease activity could be efficiently discriminated from other disease activity patients by specific protein biomarkers (m/z 2,032.31, 2,506.214, and Z9286.495). Two biomarkers (m/z 2,032.31 and 4,716.71) were applied to build the classification model for RA patients with moderate and high disease activities. Biological markers for etanercept (m/z 2,671.604064, 5,801.840579, 8,130.195641, and 9,286.49499) were observed between the responder (n = 7) and non-responder groups (n = 4) (p < 0.05).Conclusion: We successfully established a series of diagnostic models involving RA and RA with complications as well as assessed disease activity. Furthermore, we found that CCL24 may be a valuable auxiliary diagnostic indicator for RA. These results provide reference values for clinical practice in the future.

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Background: Primary Sjögren's syndrome (pSS) is an autoimmune disease that leads to the destruction of exocrine glands and formation of multisystem lesions. Abnormal proliferation, apoptosis, and differentiation of CD4+ T cells are key factors in the pathogenesis of pSS, seriously affecting the appearance, progression, and outcome of the disease. Human umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exos) may effectively simulate the immunoregulatory and tissue repair functions of MSCs while avoiding the risks associated with MSCs treatment. Hence, UCMSC-Exos treatment is expected to become a new treatment for pSS. However, if UCMSC-Exos can regulate the abnormal proliferation, apoptosis, and differentiation of CD4+ T cells in pSS and the specific underlying mechanisms remain to be elucidated. Methods: UCMSC-Exos were isolated and identified. Peripheral blood CD4+ T-cells were sorted using immunomagnetic beads. The proliferation, apoptosis, differentiation, and inflammatory factors of CD4+ T cells were determined using flow cytometry. Autophagosomes of CD4+ T cells were detected using transmission electron microscopy, autophagy-related proteins were detected using western blotting, and autophagy-related genes were detected using RT-PCR. Results: UCMSC-Exos inhibited excessive proliferation of peripheral blood CD4+ T cells in pSS patients, blocked the G0/G1 phase transition, inhibited S phase cells, suppressed excessive apoptosis of CD4+ T cells, reduced the Th17 cell ratio, elevated the regulatory T cell (Treg) ratio, restored the Th1/Th2 and Th17/Treg balance, inhibited the CD4+ T cell-associated pro-inflammatory factors IFN-γ, TNF-α, IL-6, IL-17A, and IL-17F secretion, and promoted anti-inflammatory factor IL-10 and TGF-β secretion. UCMSC-Exos reduced the elevated autophagy levels in the peripheral blood CD4+ T cells of patients with pSS. Furthermore, UCMSC-Exos regulated CD4+ T cell proliferation and early apoptosis in pSS patients through the autophagy pathway, inhibited Th17 cell differentiation, promoted Treg cell differentiation, and restored the Th17/Treg balance. Conclusions: UCMSC-Exos regulate CD4+ T cell proliferation, apoptosis, and differentiation in patients with pSS through the autophagy pathway and exhibit immunoregulatory effects. These results provide an important theoretical and experimental foundation for exploring UCMSC-Exos as a new treatment for pSS and its application in clinical transformation.

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Background: The treatment of rheumatoid arthritis (RA) has advanced considerably in the last 20 years. However, few population-based studies have assessed mortality rates and the underlying cause of death (UCD) in patients with RA and RA-associated interstitial lung disease (RA-ILD). We conducted a study to evaluate trends in mortality rates, demographic characteristics, and UCDs in patients with RA-ILD.Methods: Through data from death certificates (1999-2018) acquired from the U.S. Centers for Disease Control and Prevention Multiple Cause of Death files, we explored trends in mortality rates and UCD for RA and RA-ILD patients. We evaluated trends in crude rates and age-standardised mortality rates (ASMR) for patients with RA and RA-ILD.Results: In both RA and RA-ILD patients, ASMR variation trended downward over a 20-year period. The ASMR ratio of RA-ILD to RA decreased by 5.84%. The ASMR for RA and RA-ILD stratified by sex or age group also trended downward. The change in the ASMR ratio of RA-ILD to RA differed between men and women, trending downward in women and upward in men. Arthropathies and ILD were the two most frequent UCDs for RA-ILD, while the most frequent UCDs for RA were arthropathies and ischaemic heart disease. Conclusions: Although both RA and RA-ILD showed a downward trend in mortality, RA combined with ILD may reduce patient life span. Specifically, the mortality rate for RA-ILD remained relatively stable during the study period when ILD was the UCD, which suggests the necessity of devoting resources to active prevention, early diagnosis, and effective management of RA-ILD.