汽车制造工人颈部职业性肌肉骨骼疾患及危险因素探讨

目的调查汽车制造工人职业性肌肉骨骼疾患(WMSDs)发病情况，探讨其颈部WMSDs的危险因素。方法采用整群抽样方法，选择广州市1家汽车整车及1家零部件生产企业共8356名作业人员为研究对象，采用《北欧肌肉骨骼疾患问卷(修改版)》(NMQ)调查WMSDs患病情况，多因素Logistic回归分析颈部WMSDs影响因素，并对危险因素接触情况进行调査分析。结果研究对象WMSDs年患病率为44.6%，其中颈部WMSDs患病率为25.4%(2126/8356)，以发动机生产及总装岗位作业工人的颈部WMSDs较高，年患病率分别为30.6%、26.3%。多因素Logistic回归分析结果显示，颈部WMSDs的主要危险因素包括年龄、工龄、以不舒服的姿势工作、每天从事同样的工作、涉及到寒冷凉风或气温变化、经常加班、腰背部经常重复同一动作、颈部前倾或后仰、颈部长时间保持同一姿势。调查发现，84.9%的研究对象每天从事同样的工作，总装岗位最高(89.0%)；83.5%的作业工人经常加班；81.6%的作业工人工作中颈部前倾或后仰，以发动机生产岗位最为突出(87.5%)。结论汽车制造作业人员WMSDs患病率较高，尤以颈部最为常见，其危险因素主要包括不良工作姿势及不合理的劳动组织，发动机生产及总装岗位是颈部WMSDs的重点风险岗位，应开展有效的工效学干预措施。     

Cytokine-induced endogenous production of prostaglandin D2 is essential for human group 2 innate lymphoid cell activation

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Amino acid metabolism as drug target in autoimmune diseases

In mammals, amino acid metabolism has evolved to control immune responses. Autoimmune diseases are heterogeneous conditions that involve the breakdown of tolerogenic circuitries and consequent activation of autoreactive immune cells. Therefore, critical enzymes along amino acid degradative pathways may be hijacked to keep in check autoimmunity. We examined here current knowledge of indoleamine 2,3-dioxygenase 1 (IDO1) and arginase 1 (ARG1), the main enzymes catabolizing tryptophan and arginine, respectively, in organ-specific and systemic autoimmune diseases as well as in the development of autoantibodies to therapeutic proteins. At variance with neoplastic contexts, in which it is known to act as a pure immunosuppressive molecule, ARG1 exhibited a protective or pathogenetic profile, depending on the disease. In contrast, in several autoimmune conditions, the bulk of data indicated that drugs capable of potentiating IDO1 expression and activity may represent valuable therapeutic tools and that IDO1-based immunotherapeutic protocols could be more effective if tailored to the genetic profile of individual patients.     

B-cell-specific-peroxisome proliferator-activated receptor γ deficiency augments contact hypersensitivity with impaired regulatory B cells

Nuclear receptor peroxisome proliferator-activated receptor γ (PPAR-γ) activation can prevent immunoinflammatory disorders and diabetes. B cells play protective roles during inflammation as well. However, the roles of endogenous PPAR-γ in the regulatory properties of B cells to relieve inflammation remain unknown. Here, we developed B-cell-specific PPAR-γ knockout (B-PPAR-γ^−/−) mice and found that the conditional deletion of PPAR-γ in B cells resulted in exaggerated contact hypersensitivity (CHS). Meanwhile, interferon-γ (IFN-γ) of CD4⁺ CD8⁺ T cells was up-regulated in B-PPAR-γ^−/− mice in CHS. This showed that the regulatory function of B cells in B-PPAR-γ^−/− mice declined in vivo. Whereas splenic CD5⁺ CD1d^hi regulatory B-cell numbers and peripheral regulatory T-cell numbers were not changed in naive B-PPAR-γ^−/− mice. Loss of PPAR-γ in B cells also did not affect either CD86 or FasL expression in splenic CD5⁺ CD1d^hi regulatory B cells after activation. Notably, interleukin-10 (IL-10) production in CD5⁺ CD1d^hi regulatory B cells reduced in B-PPAR-γ-deficient mice. In addition, functional IL-10-producing CD5⁺ CD1d^hi regulatory B cells decreased in B-PPAR-γ^−/− mice in the CHS model. These findings were in accordance with augmented CHS. The current work indicated the involvement of endogenous PPAR-γ in the regulatory function of B cells by disturbing the expansion of IL-10-positive regulatory B cells.     

Are rats more human than mice?

In contrast to rats, mouse models are nowadays generally used for the investigation of immune responses and immune-mediated diseases, there are many different strains and mouse-specific tools available, and it is easy to generate transgenic and constitutive or inducible knockout mice for any gene. Many immune markers and mechanisms have been detected in mice and have been introduced as gold standard in immunology, however, some turned out to be not unconditionally transferable to the human immune system.Rats have been used more frequently in former days but are mostly outstripped by mice due to the fact that fewer strains are available, they need more space than mice, are more expensive to maintain and breed, and it is extremely difficult to generate transgenic or ko-rats. Consequently, the choice of rat-specific diagnostic tools like antibodies is quite poor and most researchers have switched to mouse models for the investigation of immune mechanisms, while rats are still widely used for toxicology by the pharmaceutical industry. However, it should be taken into consideration that there are some immunological similarities between rats and humans that are not presented in mice. Some of them like MHC class II and Foxp3 expression by activated effector T cells we have detected during our research on the immune response of rat models of experimental autoimmune uveitis.     

Fibroblast-stimulating lipopeptide-1 as a potential mucosal adjuvant enhances mucosal and systemic immune responses to enterovirus 71 vaccine

To prevent viral infection at the site of entry, mucosal vaccines are potent tools for inducing IgA secretion for defense. Because Toll-like receptor (TLR) ligands serve as strong adjuvants, two ligands that mimic the structure of mycoplasmal and bacterial lipopeptides represent interesting vaccine candidates. Pam3CSK4, a synthetic triacylated lipopeptide, interacts with TLR2/1. Because fibroblast-stimulating lipopeptide-1 (FSL-1), a synthetic diacylated lipopeptide, is recognized by TLR2/6, we targeted the potential immuno-inducibility of Pam3CSK4 and FSL-1 as adjuvants of an enterovirus 71 (EV71) mucosal vaccine. Naïve BALB/c mice were used for intranasal immunization three times over a 3-week interval, with results showing that EV71-specific IgG and IgA in serum, nasal washes, bronchoalveolar lavage fluid, and feces from the EV71 + FSL-1 group were significantly higher than levels observed in mice treated with EV71 + Pam3CSK4, EV71 alone, or the control group treated with phosphate-buffered saline. Furthermore, we observed more EV71-specific IgG and IgA-producing cells in treatments using EV71 formulated with FSL-1. Additionally, T cell-proliferative responses and interferon-γ and interleukin-17 secretion were significantly increased when inactivated EV71 was formulated using FSL-1. Moreover, serum from immunized mice was capable of neutralizing the infectivity of EV71 (C2 genotype) and was able to cross-neutralize the B4 and B5 genotypes of EV71. Our data suggested that FSL-1 could be used as an efficient adjuvant for intranasal EV71-vaccine immunization.     

Effect of Myd88 deficiency on gene expression profiling in salivary glands of female non-obese diabetic (NOD) mice

ObjectivesSjögren's syndrome (SS) is a chronic autoimmune disease characterized by inflammatory lesions in the salivary and lacrimal glands, which are caused by distinct lymphocytic infiltrates. Female non-obese diabetic (NOD) mice spontaneously develop inflammatory lesions of the salivary glands with SS-like pathological features. Previous studies have shown that MyD88, a crucial adaptor protein that activates innate immune signaling, affects lymphocytic infiltration, but its detailed role remains unclear. In this study, we investigated the role of MyD88 through gene expression profiling in the early phase of pathogenesis in the salivary glands of female NOD mice.MethodsSubmandibular glands collected from 10-week-old female wild-type and Myd88-deficient NOD mice were used for RNA preparation, followed by microarray analysis. The microarray dataset was analyzed to identify Myd88-dependent differentially expressed genes (DEGs). Data generated were used for GO enrichment, KEGG pathway, STRING database, and INTERFEROME database analyses.ResultsMyd88 deficiency was found to affect 230 DEGs, including SS-associated genes, such as Cxcl9 and Bpifa2. Most of the DEGs were identified as being involved in immunological processes. KEGG pathway analysis indicated that the DEGs were putatively involved in autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. Furthermore, the DEGs included 149 interferon (IFN)-regulated genes.ConclusionsMyD88 is involved in the expression of specific genes associated with IFN-associated immunopathological processes in the salivary glands of NOD mice. Our findings are important for understanding the role of MyD88-dependent innate immune signaling in SS manifestation.