Nucleus classification in histology images using message passing network

Identification of nuclear components in the histology landscape is an important step towards developing computational pathology tools for the profiling of tumor micro-environment. Most existing methods for the identification of such components are limited in scope due to heterogeneous nature of the nuclei. Graph-based methods offer a natural way to formulate the nucleus classification problem to incorporate both appearance and geometric locations of the nuclei. The main challenge is to define models that can handle such an unstructured domain. Current approaches focus on learning better features and then employ well-known classifiers for identifying distinct nuclear phenotypes. In contrast, we propose a message passing network that is a fully learnable framework build on classical network flow formulation. Based on physical interaction of the nuclei, a nearest neighbor graph is constructed such that the nodes represent the nuclei centroids. For each edge and node, appearance and geometric features are computed which are then used for the construction of messages utilized for diffusing contextual information to the neighboring nodes. Such an algorithm can infer global information over an entire network and predict biologically meaningful nuclear communities. We show that learning such communities improves the performance of nucleus classification task in histology images. The proposed algorithm can be used as a component in existing state-of-the-art methods resulting in improved nucleus classification performance across four different publicly available datasets.     

Biomechanical analysis of fractures in the mandibular neck (collum mandibulae)

After treatment of fractures in the neck of the mandible by means of immobilization of the dentition, often more or less severe manifestations of malocclusion remain. It was hypothesized that this is caused by an altered articulation in the jaw joint on the affected side. Furthermore, it was hypothesized that an anteriorly displaced condyle, as observed frequently as a side effect of the treatment, is caused by pull of the lateral pterygoid muscle, despite maxillomandibular fixation.Intervention experiments were performed in silico to test these hypotheses. With a biomechanical model of the human masticatory system alterations were applied mimicking a fractured mandibular neck and configurations that had been observed after healing.It was predicted that the altered articulation in the jaw joint caused asymmetrical jaw movements despite symmetrical muscle activation. The jaw was predicted to close with an open bite similar to clinical observations. The predicted laterodeviations, however, were not in accordance with clinical observations. Despite maxillo-mandibular fixation the lateral pterygoid muscle was able to pull the mandibular condyle out of its fossa in anterior direction. Consequently, despite some methodological limitations, in general the predictions corroborated the hypotheses.     

Protective effect of forsythoside B against lipopolysaccharide-induced acute lung injury by attenuating the TLR4/NF-κB pathway

Acute lung injury (ALI), which is mainly triggered by infection, pneumonia, vasculitis, and sepsis, has no specific and effective therapy except for primary supportive treatment or bedside care. Excessive inflammation caused by innate immune cells is the major characteristic of ALI. Forsythoside B, a phenylethanoside compound, possesses good antioxidant and anti-bacterial properties in vivo and in vitro. In this study, the therapeutic potential of forsythoside B and its mechanism of action were investigated in a lipopolysaccharide (LPS)-induced ALI mouse model. The results showed that LPS-induced edema exudation and lung pathological changes in mice were significantly suppressed by forsythoside B pre-treatment. Furthermore, it also attenuated lung inflammation caused by LPS stimulation, evidenced by decreased inflammatory cell infiltration and down-regulated expression of cytokines, chemokines, and inducible enzymes. The anti-inflammation property of forsythoside B was confirmed in vitro using LPS-stimulated RAW 264.7 macrophages. Moreover, it alleviated LPS-induced inflammation by inhibiting the activation of TLR4/NF-κB signaling pathway in vivo and in vitro. In conclusion, the results demonstrated that forsythoside B protects against LPS-induced ALI by attenuating inflammatory cell infiltration and suppressing TLR4/NF-κB-mediated lung inflammation. Therefore, it might be a potential therapeutic agent for ALI caused by sepsis.     

Longitudinal diffusion tensor imaging of patients with degenerative cervical myelopathy following decompression surgery

Previous studies have reported the utility of diffusion tensor imaging (DTI) as an imaging biomarker for the severity of myelopathy and subsequent surgical outcome in patients with degenerative cervical myelopathy (DCM). We hypothesized that DTI may reflect neurological recovery following surgery. The purpose of this study was to evaluate the ability of DTI to assess the post-operative alteration of neural status in patients with DCM as well as to predict post-operative recovery. We enrolled 15 patients with DCM who underwent decompression surgery. The Japanese Orthopaedic Association (JOA) score was evaluated before and 1 year after surgery. The participants were examined using DTI on a 3.0 T magnetic resonance scanner before, and 1 year after surgery. Fractional anisotropy (FA) and mean diffusivity (MD) were assessed for both time points. The correlations between the pre- and post-operative FA and MD values and the pre- and post-operative JOA scores were analyzed. Although the JOA score improved significantly after surgery from 8.9 to 12.3, there was no significant change between the pre- and post-operative FA and MD values. The post-operative outcomes after 1 year moderately correlated with the pre-operative FA values (Spearman’s ρ = 0.55, p = 0.03 and Spearman’s ρ = 0.56, p = 0.03 for change and recovery rate of the JOA score, respectively). However, there was no correlation between the post-operative FA and post-operative JOA scores nor between MD and clinical outcomes. DTI cannot be utilized as a biomarker for post-operative alterations of neural status of the spinal cord; however, pre-operative DTI may be useful as a predictor of surgical outcomes.     

Premature ovarian insufficiency and autoimmune diseases

Premature ovarian insufficiency (POI) is a clinical syndrome defined by loss of ovarian activity before the age of 40 years and has a potentially devastating effect upon women's health, both physically and psychologically. An underlying autoimmune disease has been identified in approximately 20% of patients with POI, the most common of which are disorders of the thyroid and adrenal glands. Nevertheless, in the majority of cases, the etiology is unknown. The damage mechanism to the ovary is usually caused by antibodies, and autoimmune POI is usually characterized by cellular infiltration of the theca cells of growing follicles by various inflammatory cells. Yet, other various factors and proteins of unknown clinical significance are present.The major diagnostic tool for otherwise idiopathic POI is the presence of autoantibodies against various ovarian components that strongly support the option of autoimmune etiology of POI.Treatment of the underlying cause of POI is the main strategy, although immunosuppressive therapy should be considered in a selected population of well-defined autoimmune POI and, as in idiopathic POI, in whom the resumption of ovarian activity is possible.     

Corticosterone-mediated microglia activation affects dendritic spine plasticity and motor learning functions in minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) is characterized as cognitive deficits including memory and learning dysfunctions after liver injuries or hepatic diseases. Our understandings of neurological mechanisms of MHE-associated cognitive syndromes, however, are far from complete. In the current study we generated a mouse MHE model by repetitive administrations of thioacetamide (TAA), which induced hyperammonemia plus elevated proinflammatory cytokines in both the general circulation and motor cortex. MHE mice presented prominent motor learning deficits, which were associated with excess dendritic spine pruning in the motor cortex under 2-photon in vivo microscopy. The pharmaceutical blockade of glucocorticoid receptor or suppression of its biosynthesis further rescued motor learning deficits and synaptic protein loss. Moreover, MHE mice presented microglial activation, which can be alleviated after glucocorticoid pathway inhibition. In sum, our data demonstrates corticosterone-induced microglial activation, synaptic over-pruning and motor learning impairments in MHE, providing new insights for MHE pathogenesis and potential targets of clinical interventions.     

中医心理疗法干预银屑病的应用初探

银屑病作为皮肤科一种常见疑难性疾病,病情缠绵不愈、根治困难,目前银屑病的发生与社会心理因素的关系日益密切。在长期银屑病临床研究中发现,祖国医学运用辨证施治配合辅助疗法治疗银屑病有其独特的临床疗效。结合近几年中医心理疗法治疗银屑病的研究进展,本文旨在倡导在中医整体观念的指导下辨证施治银屑病,并辅助中医心理疗法干预,综合意法、安神养形法、音乐疗法等多种方法应用于银屑病的防治中,从而达到"未病先防,既病防变"的目的,提高患者生存质量,也为银屑病的防治提供理论依据。     

Piperine attenuates lipopolysaccharide (LPS)-induced inflammatory responses in BV2 microglia

Piperine, the chief alkaloid isolated from Piper nigrum, has been known to have anti-inflammatory effect. However, the effects of piperine on neuroinflammation have not been reported. In the present study, we evaluated the effects of piperine on neuroinflammation in BV2 microglia and investigated the molecular mechanism. The results showed that piperine significantly inhibited LPS-induced TNF-α, IL-6, IL-1β, and PGE₂ production in BV2 cells. Western blot analysis showed that piperine dose-dependently inhibited LPS-induced NF-κB activation. Furthermore, piperine was found to amplify the expression of Nrf2 and HO-1 up-regulated by LPS. In addition, the inhibition of inflammatory mediators by piperine can be reversed by transfection with Nrf2 siRNA. In conclusion, piperine inhibited LPS-induced inflammatory response by activating Nrf2 signaling pathway. These results indicated that piperine may be a promising agent for the treatment of neurodegenerative diseases.