The Naturally Occurring YMDD Mutation among Patients Chronically Infected HBV and Untreated with Lamivudine: A Systematic Review and Meta-Analysis

Background: Several recent reports have demonstrated that tyrosine (Y)-methionine (M)-aspartic acid (D)-aspartic acid (D) (YMDD) motif mutations can naturally occur in chronic HBV patients without antiviral treatment such as lamivudine therapy. This paper aims to assess the overall spontaneous incidence and related risk factors of YMDD-motif mutations among lamivudine-naïve chronic HBV carriers, so as to provide some clue for clinical treatment of hepatitis B. Methodology/Principal Findings: Chinese and English literatures were searched for studies reporting natural YMDD mutations among untreated chronic HBV patients from 2001 to 2010. The incidence estimates were summarized and analyzed by meta-analyses. Forty-seven eligible articles from eight countries were selected in this review (13 in English and 34 in Chinese). The pooled incidence of YMDD-motif mutation among untreated chronic HBV patients from eight countries was 12.21 % (95 % CI: 9.69%–14.95%). China had an incidence of 13.38 % (95 % CI: 10.90%–16.07%) and seven other countries had an incidence of 9.90 % (95 % CI: 3.28%–19.55%), respectively. Lamivudine therapy would increase the risk of mutations 5.23 times higher than the untreated patients. A higher HBV DNA copy number was associated with increased incidence of natural YMDD mutation. No significant difference was found in YMDD mutation incidence between groups of different gender, age, HBeAg status, patients ’ ALT (alanine aminotransferase) level, and between the groups of HBV genotype B and C. Conclusions: The YMDD-motif mutations can occur spontaneously with a relatively high incidence in CHB patient

Method and practice of comparing indicators from standards

Chinese standards and foreign standards differ in technical indicators and requirements, which result in the poor recognition of products that comply with Chinese standards. It is crucial to set up a universal method to compare standard indicators, so that the inconsistency between standards could be eliminated, and ultimately improve Chinese products competitiveness. This paper proposed a method for indicator comparison from standards. Based on Semantic Web technology, the method introduced fragmentation of standard documents in a manner of ‘product stylistic rule indicator’ triplet. The processed fragments were annotated by the knowledge-based organization and used for the following indicator comparison. The method and procedure were generalized to develop standard indicator comparison system. The system provided a great experience in representing technical indicators as well as the comparison of indicators from standards. Further practice of the system suggested that repeated standard development and conflicted indicators in Chinese standards are still common

Method and practice of comparing indicators from standards

Chinese standards and foreign standards differ in technical indicators and requirements, which result in the poor recognition of products that comply with Chinese standards. It is crucial to set up a universal method to compare standard indicators, so that the inconsistency between standards could be eliminated, and ultimately improve Chinese products competitiveness. This paper proposed a method for indicator comparison from standards. Based on Semantic Web technology, the method introduced fragmentation of standard documents in a manner of ‘product stylistic rule indicator’ triplet. The processed fragments were annotated by the knowledge-based organization and used for the following indicator comparison. The method and procedure were generalized to develop standard indicator comparison system. The system provided a great experience in representing technical indicators as well as the comparison of indicators from standards. Further practice of the system suggested that repeated standard development and conflicted indicators in Chinese standards are still common

Disease-Specific Autoantibodies Induce Trained Immunity in RA Synovial Tissues and Its Gene Signature Correlates with the Response to Clinical Therapy

Much evidence suggests that trained immunity is inappropriately activated in the synovial tissue in rheumatoid arthritis (RA), but the underlying mechanism remains unclear. Here, we describe how RA-specific autoantibody deposits can train human monocytes to exert the hyperactive inflammatory response, particularly via the exacerbated release of tumor necrosis factor α (TNFα). Comparative transcriptomic analysis by plate-bound human IgG (cIgG) or β-glucan indicated that metabolic shift towards glycolysis is a crucial mechanism for trained immunity. Moreover, the cIgG-trained gene signatures were enriched in synovial tissues from patients with ACPA- (anticitrullinated protein antibody-) positive arthralgia and undifferentiated arthritis, and early RA and established RA bore a great resemblance to the myeloid pathotype, suggesting a historical priming event in vivo. Additionally, the expression of the cIgG-trained signatures is higher in the female, older, and ACPA-positive populations, with a predictive role in the clinical response to infliximab. We conclude that RA-specific autoantibodies can train monocytes in the inflamed lesion as early as the asymptomatic stage, which may not merely improve understanding of disease progression but may also suggest therapeutic and/or preventive strategies for autoimmune diseases

Additional file 1: Figure S1. of Diet-induced obesity alters myeloid cell populations in naĂŻve and injured lung

Adhesion Receptor Expression on Bone Marrow Leukocytes at 3 Months on HFD vs. LFD. Bone marrow cells were isolated, counted, and immunostained with anti-murine antibodies to CD45, Ly6G, CD11b, Ly6C, CD62L, ICAM-1, CXCR2, and LFA-1 and analyzed by FACS. MFI for adhesion and chemokine receptors were measured in (A) PMNs and (B) Ly6Chigh monocytes. (A) Among those receptors expressed by these cells, there was no difference in LFA-1, CD62L and CXCR2 levels in HFD vs. LFD PMNs. (B) Similarly, there was no difference in LFA-1 and CD62L expression in Ly6Chigh monocytes. (TIF 1076 kb

Additional file 2: Figure S2. of Diet-induced obesity alters myeloid cell populations in naïve and injured lung

Gating strategy for BAL and LH leukocytes. Post-LPS, lungs were lavaged for BAL cells. The lungs were also perfused to remove vascular leukocytes and processed for flow cytometry. (A) BAL and (B) LH cells from LFD (top rows) and HFD (bottom rows) mice were gated based on size (FSC) and granularity (SSC). CD45+ leukocytes were selected, and alveolar macrophages identified as CD11c+GR1− (black circle). Alveolar macrophages were also CD11blowSSChigh. PMNs were identified as GR1+F4/80−CD11b+ cells (grey box). Another population of myeloid cells in the lung was identified as GR1+F4/80+CD11b+ (blue box). (TIF 4080 kb