Inadequate induction of suppressor of cytokine signaling-1 causes systemic autoimmune diseases

Suppressor of cytokine signaling (SOCS)-1 is a cytokine-inducible, negative regulatory molecule of Janus kinases (JAK) and its deficiency causes hyper-response to various cytokines. SOCS-1(-/-) mice spontaneously develop a fatal disease depending on aberrantly activated lymphocytes. Here, we show that partial restoration of SOCS-1 in lymphoid cells rescues SOCS-1(-/-) mice from the early-onset fatal disease, indicating that SOCS-1 expression in vivo is especially required in lymphocytes. However, SOCS-1 expression in these SOCS-1-restored mutant mice (E( micro )-SOCS-1(-/-) mice) was insufficient for proper down-regulation of its target signaling, and these mice spontaneously exhibit hyperactivation of lymphocytes, an increase in the levels of serum Ig and anti-DNA autoantibodies, and glomerulonephritis with glomerular IgG deposition. These phenotypes resemble those of murine systemic autoimmune diseases, models for systemic lupus erythematosus (SLE). Interestingly, similar phenotypes were also observed in adult female SOCS-1(+/-) mice, indicating that the autoimmune phenotypes of these mice can be ascribed primarily to the inadequate expression of SOCS-1. In addition, autoimmune phenotypes were not observed in SOCS-1(+/-)CD4(-/-) mice, suggesting that autoimmunity is dependent on hyper-activated CD4(+) T cells. Our findings also suggest that insufficient expression of SOCS-1 results in impaired function of CD25(+)CD4(+) regulatory T cells, which may contribute to aberrant activation of CD4(+) T cells. These findings suggest that dysfunction of SOCS-1 can be a pathogenic factor of systemic autoimmune diseases such as SLE.     

Expression of HLA-DR antigens in inflammatory bowel disease mucosa: Role of intestinal lamina propria mononuclear cell-derived interferon γ

The expression of HLA-DR antigens on the surface of immune cells is crucial for appropriate antigen presentation and a normal immune response. In the intestinal mucosa involved by Crohn's disease and ulcerative colitis the expression of HLA-DR antigens is increased in both immune and nonimmune cells, a phenomenon probably mediated by soluble factors, such as interferon , produced by locally activated mononuclear cells. This study investigated the production of interferon by inflammatory bowel disease and control intestinal lamina propria mononuclear cells, and the ability of this endogenously produced lymphokine to induce expression of HLA-DR antigens on the monocytic cell lines U937 and ML3. After in vitro stimulation with interleukin 2 or phytohemagglutinin, but not spontaneously, lamina propria mononuclear cells produced variable amounts of interferon , and their culture supernatants could induce de novoexpression of HLA-DR antigens on the monocytic indicator cells. When the mononuclear cells were derived from inflammatory bowel disease mucosa, both the amount of interferon present in the supernatants and the number of HLA-DR-positive cells induced by these supernatants were decreased as compared to controls. These results suggest that, in inflammatory bowel disease, interferon may not be the only mediator of HLA-DR induction in the gut and that other soluble factors or agents, alone or interacting with interferon , may also be responsible for this event, resulting in the enhanced HLA-DR antigen expression observed in the inflamed intestinal mucosa.This work was supported by a grant (DK 30399) from the National Institutes of Health (NIDDK), and by the International Center for Specialty Studies of the Cleveland Clinic Foundation.     

实习护生角色宽度自我效能现状及影响因素分析

目的 探讨实习护生角色宽度自我效能现状及其影响因素,为实施针对性干预,提升实习护生群体角色宽度自我效能水平提供参考。 方法 采用一般资料调查表、角色宽度自我效能量表和心理资本量表对湖南省5所医院535名实习护生进行问卷调查。 结果 实习护生角色宽度自我效能总分为（24.27±6.64）分,心理资本总分（101.44±18.03）分;分层回归显示,获奖经历、兴趣与专业的匹配程度、医院氛围及敏感人格对实习护生角色宽度自我效能产生影响（均P＜0.05）,心理资本可独立解释角色宽度自我效能31.5%的变异。 结论 实习护生角色宽度自我效能水平较高,受多种因素影响,心理资本可正向影响实习护生角色宽度自我效能,教师和护理管理者可采取有效措施提高护生心理资本,进而提高角色宽度自我效能,稳定和发展护理队伍。     

Antioxidant Mechanism of Xiaojin Pill(小金丸) for Treatment of Peyronie's Disease in Rats Based on Matrix Metalloproteinases

Objective: To evaluate the effects of Xiaojin Pill(小金丸) in the treatment of Peyronie's disease(PD) in a rat model. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into four groups with 6 in each: sham operation, PD model, vehicle control and Xiaojin Pill groups. The rats in the sham operation group received penile tunica albsginea(TA) injection with 50 μL vehicle, while the rats in the other 3 groups received 50 μL penile TA injection of 50 μg transforming growth factor(TGF)-β1. Forty-two days after the injection, rats in the vehicle control and Xiaojin Pill groups received 0.5 mL water and Xiaojin Pill solution(107 mg/kg of body weight), respectively by gavage for 28 days, while those in the sham operation and PD model groups did not receive any intervention. After intervention, the expressions of matrix metalloproteinase 2/9(MMP2/9), nitric oxidesynthase(NOS), superoxide dismutase(SOD) and malondialdehyde(MDA) were measured. Results: Rats in the PD model and vehicle control groups presented obvious fibrosis in corpus cavernosum(CC) and demonstrated a significantly increased expressions of MMP2 and MMP9 in the CC compared with the sham operation group(all P0.01). In contrast, the expressions of MMP2 and MMP9 in the Xiaojin Pill group were significantly down-regulated(both P0.01). In addition, the levels of NOS and MDA in CC were significantly increased while the activity of SOD was decreased in the PD model and vehicle control groups compared with the sham operation group(al P0.01). After Xiaojin Pil treatment, the levels of MDA, NOS and SOD appeared to be corrected(al P0.01). Conclusions: Xiaojin Pill could reduce fibrosis in the CC by decreasing the expressions of MMPs, NOS and MDA, and by increasing the activity of SOD. Therefore, Xiaojin Pill might be a therapeutic option for PD.     

平面细胞极性在晶状体发育中的作用

晶状体发育是一个复杂的生物学过程,受多种信号分子及其构成的通路网络调控。近年研究发现,平面细胞极性(PCP)信号通路在晶状体发育过程中起重要作用,是形成晶状体正常透明度和形态的基础。PCP的深入研究为临床治疗先天性白内障提供了指导意义,同时更是有望成为完善再生晶状体的新干预靶点。本文结合目前该领域研究进展就PCP在晶状体的发育过程中的作用进行详细综述。     

A novel mutation in FBN1 gene in autosomal dominant Marfan syndrome and macular degeneration in a Chinese consanguineous family

AIM: To report a novel mutation in FBN1 gene in a Chinese consanguineous family with common Marfan syndrome (MFS) phenotype and an unusual bilateral macular degeneration. METHODS: Ophthalmic, cardiovascular and systemic examinations were performed, and genomic DNA extracted from all living family members. The 24-32 exon mutations of FBN1 gene were screened by Sanger Sequencing in all family members and 100 unrelated healthy Chinese individuals. RESULTS: In the four-generation family, classic MFS phenotypes were observed in all 5 patients, 2 of them had peculiar phenotype of bilateral macular degeneration. Mutation screening in FBN1 identified a heterozygous missense mutation (c.3932A>G, p.Y1311C) with co-segregation. This mutation was found with the MFS phenotypes in all 5 patients but not in unaffected members or unrelated controls. CONCLUSION: A Chinese consanguineous MFS family with uncommon bilateral macular degeneration and an unreported c.3932A>G mutation in FBN1 was identified. Our finding expands the FBN1 mutation spectrum and its possible role in the pathogenesis of Marfan syndrome.     

Innovative Verfahren der Vorhofflimmertherapie

Pulmonary vein isolation (PVI) is the established cornerstone in most catheter-based ablation treatment strategies for atrial fibrillation (AF); however, it is still a challenge to create contiguous, transmural and permanent ablation lesions using radiofrequency current in combination with three-dimensional mapping systems. To overcome these limitations, innovative spiral mapping and ablation catheters as well as balloon-based ablation catheters incorporating alternative energy sources, such as cryoenergy and laser were developed and evaluated and have proved their potential for safe and clinically effective PVI. In addition, novel ablation strategies, such as identification and ablation of AF-inducing foci and/or AF-perpetuating rotors using either endocardial or epicardial mapping systems were introduced and are currently under clinical evaluation. The identification and modulation of atrial ganglionic plexi (GP) and, therefore, of the autonomous nervous system is another additive ablation approach which requires further clinical evaluation.     

Lesions of the posterior limb of the internal capsule in neuromyelitis optica spectrum disorder

Posterior limb of the internal capsule lesions (PLICL) are one of the MRI features of neuromyelitis optica spectrum disorder (NMOSD). However, there is no evidence that such lesions are pathogenically related to NMOSD. We retrospectively analyzed features of PLICL in NMOSD, and other central nervous system inflammatory disorders, in 561 patients. We also examined the pathological samples of six patients. Of the 561 patients investigated, PLICL were found in 65 patients (11.6%). Lesions were bilateral in 26 cases (40%) and unilateral in 39 cases (60%). Unilateral lesions were mainly located on the left side (74.3%, 29/39). Of the 65 patients with PLICL, 46 patients had NMOSD (70.8%) and were positive for anti-aquaporin (AQP4-IgG), four had NMOSD (6.2%) and were AQP4-IgG negative, 10 patients had multiple sclerosis (MS), three patients had NMDAR encephalitis, and two had autoimmune meningoencephalitis. Of the six patients whose pathological samples were evaluated, all had PLICL and were negative for AQP4-IgG, and none had pathological NMOSD lesion features. These cases included three patients with multiple sclerosis, one with anti-N-methyl-D-aspartate receptor encephalitis, and two with autoimmune meningoencephalitis. In conclusion, PLICL are found not only in patients with NMOSD, but also in MS and other disorders.