Age and Gender Adjusted Comparison of Clinical Features between Severe Cases Infected with H7N9 and H1N1pdm Influenza A in Jiangsu Province,China

Background

Influenza H7N9 and H1N1pdm can cause severe human infections. It is important to investigate the distinguishing clinical features between these two diseases. Several studies have compared the differences in general, however, age and gender adjusted comparisons may be more useful and informative to the health professionals.

Methods

A total of 184 severe H1N1pdm patients and 37 severe H7N9 patients from Jiangsu Province were included in this analysis to perform age and gender adjusted comparison of clinical features.

Results

After adjusting age and gender, no significant differences in chronic medical conditions or treatment were found between severely ill patients with H7N9 and H1N1pdm. Severely ill patients with H7N9 had significantly longer interval from onset of illness to neuraminidase inhibitor treatment and to death. They were more likely to have complications such as acute respiratory distress syndrome (ARDS), liver and renal dysfunctions, and had a significantly higher risk of death.

Conclusion

Our results suggests that age and gender should be adjusted as important confounding factors when comparing the clinical features between severe H7N9 and H1N1pdm patients to avoid any misunderstanding regarding the differences between these two diseases particularly in terms of clinical severity and prognosis.     

The Beneficial Effects of P2X7 Antagonism in Rats with Bile Duct Ligation-induced Cirrhosis

Splanchnic angiogenesis in liver cirrhosis often leads to complications as gastroesophageal variceal hemorrhage and the treatment efficacy is adversely affected by poor portal-systemic collateral vasoresponsiveness related to nitric oxide (NO). Purinergic receptor subtype P2X₇ participates in the modulation of inflammation, angiogenesis, fibrogenesis and vasoresponsiveness, but the relevant influence in cirrhosis is unknown. Common bile duct-ligated (CBDL) or sham-operated Spraque-Dawley rats received brilliant blue G (BBG, a P2X₇ antagonist and food additive) or vehicle from the 15^th to 28^th day after operations, then hemodynamics, mesenteric angiogenesis, portal-systemic shunting, liver fibrosis, and protein expressions of angiogenic and fibrogenic factors were evaluated. The influence of oxidized ATP (oATP, another P2X₇ receptor antagonist) on the collateral vasoresponsiveness to arginine vasopressin (AVP) was also surveyed. BBG decreased superior mesenteric artery (SMA) flow, portal-systemic shunting, mesenteric vascular density, and mesenteric protein expressions of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), phospho (p)-VEGFR2, platelet-derived growth factor (PDGF), PDGF receptor beta (PDGFRβ), cyclooxygenase (COX)-1, COX-2, and endothelial NO synthase (eNOS) in CBDL rats. BBG also ameliorated liver fibrosis and down-regulated hepatic interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), PDGF, IL-1β, transforming growth factor-beta (TGF-β), p-extracellular-signal-regulated kinases (ERK), and alpha-smooth muscle actin (α-SMA) expressions in CBDL rats. The collateral vasocontractility to AVP was enhanced by oATP. oATP down-regulated eNOS, inducible NOS (iNOS), VEGF, Akt, p-Akt, and nuclear factor-kappa B (NF-κB) expressions in splenorenal shunt, the most prominent intra-abdominal collateral vessel in rodents. P2X₇ antagonism alleviates splanchnic hyperemia, severity of portal-systemic shunting, mesenteric angiogenesis, liver fibrosis, and enhances portal-systemic collateral vasoresponsiveness in cirrhotic rats. P2X₇ blockade may be a feasible strategy to control cirrhosis and complications.     

Chemical composition of Enterococcus faecalis in biofilm cells initiated from different physiologic states

Enterococcus faecalis is a ubiquitous bacterium of the gut that is observed in persistent periradicular infections. Its pathogenicity is associated with biofilm formation and the ability to survive under nutrient-poor (starvation) conditions. However, characteristics of chemical composition of biofilm cells developed by starved E. faecalis cells remain poorly understood. In this study, E. faecalis cells in exponential, stationary, and starvation phases were prepared and separately cultured to form biofilms. Confocal laser scanning microscopy was performed to verify biofilm formation. Raman microscopy was used to investigate the chemical composition of cells within the biofilms. Compared to cells in exponential or stationary phase, starved cells developed biofilms with fewer culturable cells (P?E. faecalis.     

Osteogenic role of endosomal chloride channels in MC3T3-E1 cells

PHR protein family consists of C. elegan Rpm-1/Drosophila Highwire/Zebrafish Esrom/Mouse Phr-1/Human Pam. Esrom is required for correct neurites exiting the paused state at intermediate targets as well as pteridine synthesis. This study reports the identification and characterization of two novel Esrom splice variants, named splice variants 2 (splicing out 5′ 24 bp of exon 17) and 3 (splicing out 5′ 24 bp of exons 17 and 18). Polypeptides encoded by 5′ 24 bp of exons 17 and 18 are part of basic amino-acid-rich region inside Esrom RCC1-like domain (RLD). These two splice variants maintain the whole protein reading frame and alternative exons usage patterns are conserved with mammal. At different developmental stages and adult zebrafish tissues, abundances of these splice variants are different. Importantly, by yeast two-hybrid screen and confocal colocalization analysis, it was found that alternative splicing of exon 18 regulates Esrom RLD interaction with kinesin family member 22 and G protein beta-subunit 1. Taken together, these results suggest that Esrom RLD functions are regulated by alternative splicing at temporal and spatial-specific manner.     

Dihydro-pyrano[2,3-b]pyridines and tetrahydro-1,8-naphthyridines as CB1 receptor inverse agonists: Synthesis,SAR and biological evaluation

Synthesis and structure–activity relationships of cannabinoid-1 receptor (CB1R) inverse agonists based on dihydro-pyrano[2,3-b] pyridine and tetrahydro-1,8-naphtyridine scaffolds are presented. Rat food intake and pharmacokinetic evaluation of 13g, 13i, 13k and 17a revealed these compounds to be highly efficacious orally active modulators of CB1R.     

SIAH-1 interacts with mammalian polyhomeotic homologues HPH2 and affects its stability via the ubiquitin-proteasome pathway

Polycomb Group (PcG) genes encode proteins that form large multimeric and chromatin-associated complexes implicated in the stable repression of developmentally essential genes. HPH2, the Homo sapiens polyhomeotic homologue 2, functions as one of the subunits of PcG complex 1. In our study, SIAH-1, an E3 ligase, could directly associate with HPH2 both in vitro and in vivo. Both the cysteine-rich region of SIAH-1 and the PxVxAxP motif of HPH2 were essential for the interaction. HPH2 was co-localized with SIAH-1 in nuclei. Furthermore, SIAH-1 was able to facilitate the ubiquitination and degradation of HPH2 via ubiquitin-proteasome pathway in vivo. The ubiquitination activity was severely impaired in the SIAH-1 mutant that either lost E3 ligase activity or had weakened binding ability with HPH2, strongly suggesting that SIAH-1 was the direct E3 ligase of HPH2. Thus, our results propose a novel role of SIAH-1 in regulating the expression level of HPH2 through the ubiquitin-proteasome pathway.     

A novel locus for maternally inherited human gingival fibromatosis at chromosome 11p15

Human isolated gingival fibromatosis is an oral disorder characterized by a slowly progressive benign enlargement of gingival tissues. The most common genetic form, hereditary gingival fibromatosis (HGF), is usually transmitted as an autosomal dominant trait. We report here for the first time a newly identified maternally inherited gingival fibromatosis in two unrelated Chinese families and mapped this disease locus to human chromosome 11p15 with a maximum two point LOD score of 8.70 at D11S4046 (θ = 0) for family 1 and of 6.02 at D11S1318 for family 2. Haplotype analysis placed the critical region in the interval defined by D11S1984 and D11S1338. A cluster of maternally expressed genes is within this critical region. We screened individuals in these two families for mutations for all known maternally expressed genes within this region. None was found either within the coding sequence or at the intron–exon boundary of these genes. Neither did we detect any loss of imprinting in three informative imprinted genes including H19, KCNQ1 downstream neighbor (KCNQ1DN) and cyclin-dependent kinase inhibitor 1C (CDKN1C). However, gene expression profile analysis revealed reduced expression of hemoglobin beta (HBB), hemoglobin delta (HBD), hemoglobin gamma A (HBG1) and hemoglobin gamma G (HBG2) genes at disease locus in HGF patients. This study suggests that genome imprinting might affect the development of HGF. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. Conflict Of Interest Statement: No competing financial interests.     

大黄醇提液抗家兔实验性高脂血症及脂肪肝的实验研究

目的:检验大黄醇提液抗家兔实验性高脂血症及脂肪肝的影响。方法:将30只雄性健康白兔随机分为5组(n=6):对照组给予基础饲料;模型组给予高脂饲料;三个大黄组给予高脂饲料同时分别灌胃不同药量的大黄醇提液。实验过程中进行一般性指标观测,检测不同阶段五组家兔血脂水平,检测脂肪肝病变程度。结果:大黄醇提液具有降低血清甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C),升高高密度脂蛋白胆固醇(HDL-C),降低肝细胞脂肪变性的作用。并且大黄醇提液的以上作用存在一定的量效关系。结论:大黄醇提液可降低动脉粥样硬化兔模型的血脂水平、降低脂肪肝的发生发展。