Polyneuropathy as Novel Initial Manifestation in a Case of “Nonsecretory” POEMS Syndrome with Sjögren’s Syndrome

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is a paraneoplastic syndrome driven by plasma cell dyscrasias. We report a patient with novel initial manifestation of polyneuropathy, which was considered due to Sjögren’s syndrome but with poor response to methylprednisolone (120 mg/d) and intravenous immunoglobulin (IVIg). Further investigation by imaging tests and following biopsy eventually confirmed the diagnosis of POEMS syndrome secondary to solitary plasmocytoma. To our knowledge, this is the first reported case of POEMS syndrome with Sjögren’s syndrome occurring in the absence of a peripheral monoclonal gammopathy, highlighting the diagnostic challenges posed by this disease and reviewing the diagnostic role of (18) F-FDG PET/CT in POEMS syndrome

Interleukin-22 Inhibits Bleomycin-Induced Pulmonary Fibrosis

Pulmonary fibrosis is a progressive and fatal fibrotic disease of the lungs with unclear etiology. Recent insight has suggested that early injury/inflammation of alveolar epithelial cells could lead to dysregulation of tissue repair driven by multiple cytokines. Although dysregulation of interleukin- (IL-) 22 is involved in various pulmonary pathophysiological processes, the role of IL-22 in fibrotic lung diseases is still unclear and needs to be further addressed. Here we investigated the effect of IL-22 on alveolar epithelial cells in the bleomycin- (BLM-) induced pulmonary fibrosis. BLM-treated mice showed significantly decreased level of IL-22 in the lung. IL-22 produced γδT cells were also decreased significantly both in the tissues of lungs and spleens. Administration of recombinant human IL-22 to alveolar epithelial cell line A549 cells ameliorated epithelial to mesenchymal transition (EMT) and partially reversed the impaired cell viability induced by BLM. Furthermore, blockage of IL-22 deteriorated pulmonary fibrosis, with elevated EMT marker (α-smooth muscle actin (α-SMA)) and overactivated Smad2. Our results indicate that IL-22 may play a protective role in the development of BLM-induced pulmonary fibrosis and may suggest IL-22 as a novel immunotherapy tool in treating pulmonary fibrosis

Activation of Sirt1 by Resveratrol Inhibits TNF-α Induced Inflammation in Fibroblasts

Inflammation is one of main mechanisms of autoimmune disorders and a common feature of most diseases. Appropriate suppression of inflammation is a key resolution to treat the diseases. Sirtuin1 (Sirt1) has been shown to play a role in regulation of inflammation. Resveratrol, a potent Sirt1 activator, has anti-inflammation property. However, the detailed mechanism is not fully understood. In this study, we investigated the anti-inflammation role of Sirt1 in NIH/3T3 fibroblast cell line. Upregulation of matrix metalloproteinases 9 (MMP-9), interleukin-1beta (IL-1β), IL-6 and inducible nitric oxide synthase (iNOS) were induced by tumor necrosis factor alpha (TNF-α) in 3T3 cells and resveratrol suppressed overexpression of these pro-inflammatory molecules in a dose-dependent manner. Knockdown of Sirt1 by RNA interference caused 3T3 cells susceptible to TNF-α stimulation and diminished anti-inflammatory effect of resveratrol. We also explored potential anti-inflammatory mechanisms of resveratrol. Resveratrol reduced NF-κB subunit RelA/p65 acetylation, which is notably Sirt1 dependent. Resveratrol also attenuated phosphorylation of mammalian target of rapamycin (mTOR) and S6 ribosomal protein (S6RP) while ameliorating inflammation. Our data demonstrate that resveratrol inhibits TNF-α-induced inflammation via Sirt1. It suggests that Sirt1 is an efficient target for regulation of inflammation. This study provides insight on treatment of inflammation-related diseases

Analysis of the Composition of Deinagkistrodon acutus Snake Venom Based on Proteomics, and Its Antithrombotic Activity and Toxicity Studies

There is a strong correlation between the composition of Deinagkistrodon acutus venom proteins and their potential pharmacological effects. The proteomic analysis revealed 103 proteins identified through label-free proteomics from 30 different snake venom families. Phospholipase A2 (30.0%), snaclec (21.0%), antithrombin (17.8%), thrombin (8.1%) and metalloproteinases (4.2%) were the most abundant proteins. The main toxicity of Deinagkistrodon acutus venom is hematotoxicity and neurotoxicity, and it acts on the lung. Deinagkistrodon acutus venom may have anticoagulant and antithrombotic effects. In summary, the protein profile and related toxicity and pharmacological activity of Deinagkistrodon acutus venom from southwest China were put forward for the first time. In addition, we revealed the relationship between the main toxicity, pharmacological effects, and the protein components of snake venom

The Agreement Between Virtual Patient and Unannounced Standardized Patient Assessments in Evaluating Primary Health Care Quality: Multicenter, Cross-sectional Pilot Study in 7 Provinces of China

BackgroundThe unannounced standardized patient (USP) is the gold standard for primary health care (PHC) quality assessment but has many restrictions associated with high human and resource costs. Virtual patient (VP) is a valid, low-cost software option for simulating clinical scenarios and is widely used in medical education. It is unclear whether VP can be used to assess the quality of PHC. ObjectiveThis study aimed to examine the agreement between VP and USP assessments of PHC quality and to identify factors influencing the VP-USP agreement. MethodsEleven matched VP and USP case designs were developed based on clinical guidelines and were implemented in a convenience sample of urban PHC facilities in the capital cities of the 7 study provinces. A total of 720 USP visits were conducted, during which on-duty PHC providers who met the inclusion criteria were randomly selected by the USPs. The same providers underwent a VP assessment using the same case condition at least a week later. The VP-USP agreement was measured by the concordance correlation coefficient (CCC) for continuity scores and the weighted κ for diagnoses. Multiple linear regression was used to identify factors influencing the VP-USP agreement. ResultsOnly 146 VP scores were matched with the corresponding USP scores. The CCC for medical history was 0.37 (95% CI 0.24-0.49); for physical examination, 0.27 (95% CI 0.12-0.42); for laboratory and imaging tests, –0.03 (95% CI –0.20 to 0.14); and for treatment, 0.22 (95% CI 0.07-0.37). The weighted κ for diagnosis was 0.32 (95% CI 0.13-0.52). The multiple linear regression model indicated that the VP tests were significantly influenced by the different case conditions and the city where the test took place. ConclusionsThere was low agreement between VPs and USPs in PHC quality assessment. This may reflect the “know-do” gap. VP test results were also influenced by different case conditions, interactive design, and usability. Modifications to VPs and the reasons for the low VP-USP agreement require further study

Resveratrol Inhibited inflammation in a Sirt1 dependent manner.

<p><b>A.</b> Western blotting analysis shows Sirt1 siRNA (20 nM) transfection for 72 hours strikingly blocked Sirt1 expression, compared to control (Cont) siRNA (20 nM) or DDW transfection. <b>B.</b> After Sirt1 or control siRNA transfection for 72 h, cells were h pretreated with resveratrol (50 nM) in the presence of TNF-α (10 ng/ml) treatment for 24 h, MMP-9 expression in the medium were examined by gelatin zymography. <b>C.</b> Cells were processed as (B) for 6 h, real-time RT-PCR analysis was used to examine mRNA expression of MMP-9, IL-6, iNOS (n = 3 per group, *<i>p</i><0.05 vs. Sirt1 siRNA-; **<i>p</i><0.01 vs. Sirt1 siRNA-).</p