The Evolutions of Medical Building Network Structure for Emerging Infectious Disease Protection and Control

Emerging infectious disease is one of the most minatory threats in modern society. A perfect medical building network system need to be established to protect and control emerging infectious disease. Although in China a preliminary medical building network is already set up with disease control center, the infectious disease hospital, infectious diseases department in general hospital and basic medical institutions, there are still many defects in this system, such as simple structural model, weak interoperability among subsystems, and poor capability of the medical building to adapt to outbreaks of infectious disease. Based on the characteristics of infectious diseases, the whole process of its prevention and control and the comprehensive influence factors, three-dimensional medical architecture network system is proposed as an inevitable trend. In this conception of medical architecture network structure, the evolutions are mentioned, such as from simple network system to multilayer space network system, from static network to dynamic network, and from mechanical network to sustainable network. Ultimately, a more adaptable and corresponsive medical building network system will be established and argued in this paper.     

Analysis of Risk Factors of Hemorrhagic Transformation After Acute Ischemic Stroke: Cerebral Microbleeds Do Not Correlate with Hemorrhagic Transformation

To study the potential risk factors including cerebral microbleeds (CMB) of hemorrhagic transformation (HT) after acute ischemic stroke. We included 348 consecutive patients with acute infarction who were hospitalized in two centers from June 2009 to December 2010. Acute ischemic infarctions were subdivided into atherosclerotic, cardioemblic, lacunar, and undetermined infarction groups. The related risk factors were recruited for analysis. All patients underwent gradient-echo T2-weighted imaging (GRE) to detect CMB and HT. Logistic regression analysis was used to analyze relationships, with HT as response variable and potential risk factors as explanatory variables. Multivariate logistic regression analysis demonstrated that predictor factors of HT were cardioembolic infarction (OR 24.956, 95 % CI 2.734–227.801, P = 0.004), infarction of undetermined causes (OR 19.381, 95 % CI 1.834–205.104, P = 0.014), and scores of NIHSS (OR 1.187, 95 % CI 1.109–1.292, P < 0.001), diabetes mellitus (OR 4.973, 95 % CI 2.004–12.338, P = 0.001). Whereas, the level of low-density lipoprotein was the protective factor (OR 0.654, 95 % CI 0.430–0.996, P = 0.048).The prevalence of CMB was 45.98 % (160/348) with no statistically difference among different subtypes. Thirty-five out of 348 (10.06 %) patients with ischemic stroke developed HT with a statistical difference among different subtypes of ischemia (χ ² = 42.140, P < 0.001). The distributions of HI and PH among subgroups were variable with significant differences (χ ² = 17.536, P = 0.001; χ ² = 12.028, P = 0.007). PH frequency of cardioembolism was the highest (4/28, 14.29 %), and symptomatic ICH was also highest (7.14 %). The CMBs do not significantly correlate with HT. Knowledge of the risk factors associated with HT after ACI, especially HT following thrombolyitc therapy may provide insight into the mechanisms underlying the development of HT, helps to develop treatment strategy that reduces the risk of PH and implicates for the design of future acute ischemic stroke trials.     

Protective Effect of Phosphatidylcholine on Restoration of Ethanol-Injured Hepatocytes Related with Caveolin-1

The absorption of phospholipid may improve the fluidity of membrane and enzyme activities. Phospholipids also play a role in promoting Caveolae formation and membrane synthesis. Caveolin-1 has a significant effect on signaling pathways involved in regulating cell proliferation and stress responsiveness. Thus, we can speculate that Caveolin-1 could affect the sense of environmental stress. We use Chang liver cell line to investigate the ability of Caveolin-1 to modulate the cellular response to ethanol injury. Caveolin-1 downregulate cells (Cav-1^?/?) were established by stable transfecting with psiRNA-CAV1 plasmids, which were more sensitive to toxic effects of ethanol than the untransfected parental cells (WT). Releasing of ALT and electric conductivity were changed significantly in Cav-1^?/? cells compared with WT. Caveolin-1 gene silencing could obviously down-regulate the activities of protein kinase C-α (PKC-α) and phospho-p42/44 MAP kinase, indicating cell proliferation and self-repairing abilities were inhibited. However, the levels of Caveolin-1 and PKC-α were increased by phosphatidylcholine administration. The results indicated that the inhibition of lipid peroxidation by phosphatidylcholine could lead to the prevention of membrane disruption, which closely correlated with the level of Caveolin-1. Since the protective effects of phosphatidylcholine against ethanol-induced lipid peroxidation might be regulated by phospholipid-PKC-α signaling pathway, related with Caveolin-1, the potential effects of phosphatidylcholine on membranes need to be verified.     

Knockdown of phosphotyrosyl phosphatase activator induces apoptosis via mitochondrial pathway and the attenuation by simultaneous tau hyperphosphorylation

Phosphotyrosyl phosphatase activator (PTPA) is decreased in the brains of Alzheimer's disease (AD) and the AD transgenic mouse models. Here, we investigated whether down‐regulation of PTPA affects cell viability and the underlying mechanisms. We found that PTPA was located in the integral membrane of mitochondria, and knockdown of PTPA induced cell apoptosis in HEK293 and N2a cell lines. PTPA knockdown decreased mitochondrial membrane potential and induced Bax translocation into the mitochondria with a simultaneous release of Cyt C, activation of caspase‐3, cleavage of poly (DNA ribose) polymerase (PARP), and decrease in Bcl‐xl and Bcl‐2 protein levels. Over‐expression of Protein phosphatase 2A (PP2A) catalytic subunit (PP2A_C) did not rescue the apoptosis induced by PTPA knockdown, and PTPA knockdown did not affect the level of and their phosphorylation of mitogen‐activated protein kinases (MAPKs), indicating that PP2A and MAPKs were not involved in the apoptosis induced by PTPA knockdown. In the cells with over‐expression of tau, PTPA knockdown induced PP2A inhibition and tau hyperphosphorylation but did not cause significant cell death. These data suggest that PTPA deficit causes apoptotic cell death through mitochondrial pathway and simultaneous tau hyperphosphorylation attenuates the PTPA‐induced cell death.

     

The Prognostic Value of Plasma Soluble ST2 in Hospitalized Chinese Patients with Heart Failure

Background

sST2 has been shown to be a risk predictor in heart failure (HF). Our aim was to explore the characteristics and prognostic value of soluble ST2 (sST2) in hospitalized Chinese patients with HF.

Methods and Results

We consecutively enrolled 1528 hospitalized patients with HF. Receiver operating characteristic (ROC) and multivariable Cox proportional hazards analysis were used to assess the prognostic values of sST2. Adverse events were defined as all-cause death and cardiac transplantation. During a median follow-up of 19.1 months, 325 patients experienced adverse events. Compared with patients free of events, sST2 concentrations were significantly higher in patients with events (P<0.001). Univariable and multivariable Cox regression analyses showed sST2 concentrations were significantly associated with adverse events (per 1 log unit, adjusted hazard ratio 1.52, 95% confidence interval: 1.30 to 1.78, P<0.001). An sST2 concentration in the highest quartiles (>55.6 ng/mL) independently predicted events in comparison to the lowest quartile (≤25.2 ng/mL) when adjusted by multivariable model. In ROC analysis, the area under the curve for sST2 was not different from that for NT-proBNP in short and longer term. Over time, sST2 also improved discrimination and reclassification of risk beyond NT-proBNP.

Conclusions

sST2 is a strong independent risk predictor in Chinese patients hospitalized with HF and can significantly provide additional prognostic value to NT-proBNP in risk prediction.     

Scorpion Venom Heat-Resistant Peptide (SVHRP) Enhances Neurogenesis and Neurite Outgrowth of Immature Neurons in Adult Mice by Up-Regulating Brain-Derived Neurotrophic Factor (BDNF)

Scorpion venom heat-resistant peptide (SVHRP) is a component purified from Buthus martensii Karsch scorpion venom. Although scorpions and their venom have been used in Traditional Chinese Medicine (TCM) to treat chronic neurological disorders, the underlying mechanisms of these treatments remain unknown. We applied SVHRP in vitro and in vivo to understand its effects on the neurogenesis and maturation of adult immature neurons and explore associated molecular mechanisms. SVHRP administration increased the number of 5-bromo-2’-dexoxyuridine (BrdU)-positive cells, BrdU- positive/neuron-specific nuclear protein (NeuN)-positive neurons, and polysialylated-neural cell adhesion molecule (PSA-NCAM)-positive immature neurons in the subventricular zone (SVZ) and subgranular zone (SGZ) of hippocampus. Furthermore immature neurons incubated with SVHRP-pretreated astrocyte-conditioned medium exhibited significantly increased neurite length compared with those incubated with normal astrocyte-conditioned medium. This neurotrophic effect was further confirmed in vivo by detecting an increased average single area and whole area of immature neurons in the SGZ, SVZ and olfactory bulb (OB) in the adult mouse brain. In contrast to normal astrocyte-conditioned medium, higher concentrations of brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF) was detected in the conditioned medium of SVHRP-pretreated astrocytes, and blocking BDNF using anti-BDNF antibodies eliminated these SVHRP-dependent neurotrophic effects. In SVHRP treated mouse brain, more glial fibrillary acidic protein (GFAP)-positive cells were detected. Furthermore, immunohistochemistry revealed increased numbers of GFAP/BDNF double-positive cells, which agrees with the observed changes in the culture system. This paper describes novel effects of scorpion venom-originated peptide on the stem cells and suggests the potential therapeutic values of SVHRP.     

Phosphoproteomic Profiling of Selenate-Treated Alzheimer's Disease Model Cells

The reversible phosphorylation of proteins regulates most biological processes, while abnormal phosphorylation is a cause or consequence of many diseases including Alzheimer''s disease (AD). One of the hallmarks of AD is the formation of neurofibrillary tangles (NFTs), which is composed of hyperphosphorylated tau proteins. Sodium selenate has been recently found to reduce tau hyperphosphorylation and NFTs formation, and to improve spatial learning and motor performance in AD mice. In the current study, the phosphoproteomics of N2aSW cells treated with selenate were investigated. To avoid missing low-abundance phosphoproteins, both the total proteins of cells and the phosphor-enriched proteins were extracted and subjected to the two-dimensional gel electrophoresis with Pro-Q diamond staining and then LC-MS/MS analysis. A total of 65 proteins were altered in phosphorylation level, of which 39 were up-regulated and 26 were down-regulated. All identified phosphoproteins were bioinformatically annotated according to their physiochemical features, subcellular location, and biological function. Most of these significantly changed phosphoproteins are involved in crucial neural processes such as protesome activity, oxidative stress, cysteine and methionine metabolism, and energy metabolism. Furthermore, decreases were found in homocysteine, phosphor-tau and amyloid β upon selenate treatment. Our results suggest that selenate may intervene in the pathological process of AD by altering the phosphorylation of some key proteins involved in oxidative stress, energy metabolism and protein degradation, thus play important roles in maintaining redox homeostasis, generating ATP, and clearing misfolded proteins and aggregates. The present paper provides some new clues to the mechanism of selenate in AD prevention.     

蓝细菌光敏色素的分子结构、生物合成和可逆光致变色效应

蓝细菌光敏色素(CBCRs)是蓝细菌中感受光的重要光受体,能够响应从紫外光到红外光范围内的光信号,进而影响蓝细菌的光化学行为。蓝细菌光敏色素通过N-末端GAF(cGMP phosphodiesterase,adenylyl cyclase and FhlA domain)结构域中保守性半胱氨酸共价结合藻胆色素,形成具有感光生理功能的色素蛋白质。本文重点在分子水平上综述了蓝细菌光敏色素的分子结构、生物合成和可逆光致变色效应机理,并基于最新的研究进展,就蓝细菌光敏色素今后的研究方向进行了展望。