The efficacy and mechanism for action of iguratimod in primary Sjögren's syndrome patients.

PURPOSE: Primary Sjögren's syndrome (pSS) has been proven as a systemic autoimmune disorder (such as Sjogren's syndrome dry eye). This research aimed to evaluate potential treating effects of Iguratimod on pSS. METHODS: Fifty pSS patients were enrolled and randomly divided into Conventional group and Iguratimod group. Improvement in pSS was evaluated every 4 weeks. pSS disease activity was evaluated with European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI). Symptoms were evaluated by determining EULAR Sjögren's syndrome patient-reported index (ESSPRI), platelet (PLT), IgG and Schirmer I test. Peripheral blood B cell molecules (CD135, IgD, CD38, CD20) and human B cell-activating factor-receptor (BAFF-R) were analyzed with flow cytometry. RESULTS: After treating for 12-weeks, pSS patients in Iguratimod and Conventional group showed a significant decrease in disease activity (ESSPRI, ESSDAI, PLT, IgG and Schirmer I test) comparing with baselines. Patients' ESSPRI (2.92 ± 0.19) and disease activity of ESSDAI (4.32 ± 0.29), PLT (95.64 ± 1.86), IgG (13.0 ± 0.45) and Schirmer I test (4.67 ± 0.31) in Iguratimod group were significantly lower compared to Conventional group (4.64 ± 0.15, 5.8 ± 2.08, 77.44 ± 1.41, 16.5 ± 0.44 and 2.25 ± 0.11) (p < 0.0001). Changes of ESSPRI, ESSDAI, PLT, IgG and Schirmer I test were remarkable observed between two groups (p < 0.001). Iguratimod and Conventional treatment demonstrated a significant reduction in total B cells in pSS patients compared with pre-treatment. The pSS patients from Iguratimod and Conventional group showed a significant decreased BAFF-R (61.82 ± 1.52, 74.07 ± 1.11) and CD38+IgD+ (48.08 ± 0.92, 62.66 ± 1.12) on B cells after treatment compared with baseline (92.26 ± 0.32, 91.53 ± 0.45, 84.39 ± 0.59, 85.04 ± 0.46) (p < 0.001). After treating 12 weeks, BAFF-R, CD38+IgD+ expression in Iguratimod group decreased significantly compared to Conventional group (p < 0.001). CONCLUSIONS: Iguratimod alleviated symptoms and mediated adaptive-immunity balance by suppressing BAFF-R positive B cell in pSS patients.

Effect of early life stress on anxiety and depressive behaviors in adolescent mice.

INTRODUCTION: Adolescence is a critical period for physical and mental development. The effect of early life stress on mood disorders has been intensively studied in adults using rodent models, but it has been less studied in adolescents. The present study aimed to examine the effect of early life stress on anxiety-related and depression-like behaviors in adolescent C57BL/6 mice and the sex difference. METHODS: C57BL/6 mice of both sexes were used, and early life stressors included maternal separation (MS, P2-12, 4 hr per day), restraint stress (RS, P33 to 39, 4 hr per day), and their combination (MRS). Open field test, elevated plus maze, and forced swimming test were performed at different time points during adolescence and adulthood. RESULTS: It was found that MS did not affect the anxiety-related behaviors of both males and females tested on P30-31 and P41-42. RS decreased the anxiety level in adolescent males but did not affect it in the females. MS, RS, and MRS all significantly increased the depression-like behavior in adolescent males, but only MRS increased the depression-like behavior in adolescent females. All effects on adolescent males and females did not persist into adulthood. CONCLUSION: The present results showed that early life stress affected anxiety-related and depression-like behavior in adolescent mice in manners depending on the nature of stress, the developmental period, and sex.

Impact of contrast-enhanced transcranial Doppler ultrasound diagnosis for young adult with cryptogenic stroke: A protocol of systematic review.

BACKGROUND: This study aims to assess the impact of contrast-enhanced transcranial Doppler ultrasound (cTCD) diagnosis for young adult with cryptogenic stroke (CS). METHODS: This study will analyze data from case-controlled studies investigating the impact of cTCD diagnosis for young adult with CS. A comprehensive literature search will be performed from PUBMED, EMBASE, Cochrane Library, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and Wanfang Data from their inceptions up to the August 1, 2019. All databases will be searched with no language limitations. Two researchers will independently carry out study selection, data collection, and study quality assessment. Any discrepancies between two researchers will be solved by a third researcher. We will apply RevMan 5.3 software and Stata 12.0 software for statistical analysis. RESULTS: Outcomes consist of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for determination of cTCD diagnosis for young adult with CS. CONCLUSION: The results of this study may summarize up-to-date evidence of cTCD diagnosis for young adult with CS. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019145641.

Proteomic analysis of plasma from rheumatoid arthritis patients with mild cognitive impairment.

Rheumatoid arthritis (RA) patients may suffer from comorbid neuropsychiatric symptoms including mild cognitive impairment (MCI). Although comorbidity of MCI is common, there are currently no validated plasma biomarkers to aid MCI diagnosis. This study screened plasma from patients with RA with and without comorbid MCI to identify potential biomarkers useful in the differential diagnosis of comorbid MCI. Plasma samples were collected from patients with RA without comorbid MCI, with comorbid MCI, and from healthy controls. Plasma samples were examined by tandem mass tags (TMT) combined with two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MSMS) to analyze protein expression. Differentially expressed proteins were identified by bioinformatics and validated by enzyme-linked immunosorbent assay (ELISA). A total of 746 reliable proteins and 158 differentially expressed proteins were identified. Fourteen patients with RA-MCI showed differential protein expression (six proteins upregulated and eight proteins downregulated) compared with those patients without MCI and with healthy controls. Bioinformatics analysis showed that the differentially expressed proteins were primarily involved in biological processes, such as cell adhesion, coagulation, apoptosis, and body fluid regulation. The results of the ELISA experiments, similar to those of the proteomic analysis, demonstrated that sonic hedgehog (SHH) was upregulated and serum paraoxonase (TTR) was downregulated in patients with RA-MCI. These results indicate that SHH and TTR may be candidate plasma biomarkers that could be used to distinguish patients with RA and comorbid MCI from those without comorbid MCI.

Pre-surgery beliefs about pain and surgery as predictors of acute and chronic post-surgical pain: A prospective cohort study.

BACKGROUND: Chronic pain post-surgical pain (CPSP) is common and has far-reaching negative consequences for patients, yet relatively few studies have evaluated the impact of both deficit- and resource-based beliefs about pain and surgery on subjective intensities of acute and chronic post-surgical pain. To address this issue a prospective cohort study was performed. METHOD: 259 consecutive surgery patients from general surgery, gynecology, and thoracic departments completed a self-report battery of demographics, pain experiences, and psychological factors 24 h before surgery (T1) and provided follow-up pain intensity ratings 48 h-72 h after surgery (T2), and at a 4-month follow-up (T3). RESULTS: In the hierarchical regression model for acute post-operative pain intensity, pre-surgery pain self-efficacy beliefs made a significant unique contribution independent of all other pre-surgery and surgery-related factors (i.e., age, presence of pre-surgical pain, type of anesthesia, surgery duration). In the prediction model for intensity of chronic post-surgical pain, beliefs about long-term effects of surgery had a unique impact after controlling other significant pre-surgery and surgery influences (gender, education, surgery time). CONCLUSION: Results underscored the potential utility of considering specific pre-surgery pain- and surgery-related beliefs as factors that predict patient experiences of acute and chronic post-operative pain.

Identifying At-Risk Subgroups for Acute Postsurgical Pain: A Classification Tree Analysis.

Objective: Acute postsurgical pain is common and has potentially negative long-term consequences for patients. In this study, we evaluated effects of presurgery sociodemographics, pain experiences, psychological influences, and surgery-related variables on acute postsurgical pain using logistic regression vs classification tree analysis (CTA). Design: The study design was prospective. Setting: This study was carried out at Chongqing No. 9 hospital, Chongqing, China. Subjects: Patients (175 women, 84 men) completed a self-report battery 24 hours before surgery (T1) and pain intensity ratings 48-72 hours after surgery (T2). Results: An initial logistic regression analysis identified pain self-efficacy as the only presurgery predictor of postoperative pain intensity. Subsequently, a classification tree analysis (CTA) indicated that lower vs higher acute postoperative pain intensity levels were predicted not only by pain self-efficacy but also by its interaction with disease onset, pain catastrophizing, and body mass index. CTA results were replicated within a revised logistic regression model. Conclusions: Together, these findings underscored the potential utility of CTA as a means of identifying patient subgroups with higher and lower risk for severe acute postoperative pain based on interacting characteristics.