Ongoing Spillover of Hantaan and Gou Hantaviruses from Rodents Is Associated with Hemorrhagic Fever with Renal Syndrome (HFRS) in China

Peer reviewe

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011

Functions of Ca2+-Binding Protein 5 in Excitable Cells

鈣離子結合蛋白 (Ca2+-binding protein 1-5, CaBP1-5) 是一群與calmodulin有高度相似性結構的蛋白質，目前僅知CaBP1及CaBP4會調控鈣離子通道的活性，而其它蛋白的功能則尚不清楚。本篇報告中，我們以PCR技術從大鼠 (Rattus norvegicus) 胚胎的大腦組織中選殖出CaBP5基因，再予以表現於兩類型興奮性細胞中，來探討其對刺激-分泌耦合機轉的調控。細胞螢光染色結果顯示，CaBP5-EYFP主要分布於細胞質中，有些則會集中於細胞核。利用細胞電生理技術，我們發現 CaBP5的大量表現會使神經細胞的鈣離子通道的開啟降低至較負電位，失去第一個 EF-hand正常功能的突變型 (5EF1) 則沒有作用。但在牛腎上腺嗜鉻細胞 (bovine chromaffin cell) 中，CaBP5對其鈣離子通道沒有同樣影響，藉由測量細胞膜電容的變化發現CaBP5的表現，也不會影響胞吐和胞吞作用。在牛腎上腺嗜鉻細胞中，CaBP5對鈣離子通道沒有同樣的作用，也沒有對胞吐 (exocytosis) 和胞吞作用 (endocytosis) 造成明顯的影響；另外，CaBP5對鈉離子電流沒有影響，但5EF1的表現增強了鈉離子電流。以上觀察顯示CaBP5可能參與神經細胞膜的鈣離子電流調控，而對鈉離子電流的影響不明顯；但在牛腎上腺嗜鉻細胞，5EF1增強了鈉離子電流的大小。Ca2+ -binding proteins 1-5 (CaBP1-5) are a group of proteins with structure similar to calmodulin. CaBP1 and CaBP4 have been reported to modulate the Ca2+ currents and synaptic plasticity of neurons; however, functions of other proteins have not been extensively investigated. In this report, functions of CaBP5 in excitable cells were studied. CaBP5 was cloned from rat (Rattus norvegicus) embryonic brain tissue and inserted into pEYFP-N1 for expression. Normally it was localized in the cytosol, but it may concentrat in the nucleus in some cells. We applied whole-cell patch clamping technique to monitor the electrophysiological properties of excitable cells. The results show that CaBP5 shifted the activation of Ca2+ channels to hyperpolarized voltages in primary neuron culture, but mutant CaBP5 with the first nonfunctional EF-hand didn’t have the same effect. When CaBP5 was expressed in cultured bovine adrenal chromaffin cells, neither the Ca2+ currents nor the exocytosis was affected, but the Na+ currents were enhanced. These observations indicate that CaBP5 may be involved in regulation of Ca2+ channels in neurons but enhanced Na+ currents in chromaffin cells.1.摘要 1.1 中文摘要..................................................... 1 1.2 英文摘要.....................................................2 2.前言 2.1 Calmodulin...................................................3 2.2 鈣離子結合蛋白...............................................4 2.3 實驗目標.....................................................5 3. 材料與方法 3.1 溶液........................................................ 7 3.2 RNA 製備與 cDNA 合成..................................... 7 3.3 CaBP5 轉接入 pEYFP-N1 載體與核苷酸點突變合成.............8 3.4 神經細胞與牛腎上腺嗜鉻細胞培養...............................9 3.5 基因轉殖 (Gene Transfection) 與細胞螢光染色................... 9 3.6 細胞電生理技術..............................................10 3.7 統計分析....................................................11 4. 結果 4.1 CaBP5 表現於大鼠的視網膜與胎鼠的大腦組織中................ 12 4.2 CaBP5 主要是均勻分布於神經細胞中，少數集中於細胞核內...... 12 4.3 CaBP5使神經細胞的鈣離子通道的開啟降低至較負電位...........13 4.4 CaBP5對神經細胞的鈉離子電流沒有影響.......................13 4.5 CaBP5 對牛腎上腺嗜鉻細胞的鈣離子電流沒有同樣影響.......... 14 4.6 CaBP5對牛腎上腺嗜鉻細胞的鈉離子電流有增強的效果........... 14 4.7 CaBP5 對牛腎上腺嗜鉻細胞的胞吐和胞吞作用沒有影響.......... 15 5. 討論...........................................................16 6. 致謝...........................................................20 7. 圖表...........................................................21 8. 參考文獻...................................................... 3

Partial Inhibition of HO-1 Attenuates HMP-Induced Hepatic Regeneration against Liver Injury in Rats

We found better liver graft regeneration with hypothermic machine perfusion (HMP) compared with static cold storage (SCS) for the first time in our pilot study, but the underlying mechanisms are unknown. Upregulated heme oxygenase- (HO-) 1 expression has been reported to play a pivotal role in promoting hepatocyte proliferation. Here, we evaluated the novel role of HO-1 in liver graft protection by HMP. Rats with a heterozygous knockout of HO-1 (HO-1+/−) were generated and subjected to 3 h of SCS or HMP pre-half-size liver transplantation (HSLT) in vivo or 6 h of SCS or HMP in vitro; control rats were subjected to the same conditions (HO-1+/+). We found that HSLT induced significant elevation of the HO-1 protein level in the regenerated liver and that HO-1 haplodeficiency resulted in decreased proliferation post-HSLT. Compared with SCS, HMP induced significant elevation of the HO-1 protein level along with better liver recovery, both of which were reduced by HO-1 haplodeficiency. HO-1 haplodeficiency-induced decreased proliferation was responsible for the attenuated regenerative ability of HMP. Mechanistically, HO-1 haploinsufficiency resulted in suppression of hepatocyte growth factor (HGF)/Akt activity. Our results suggest that inhibition of HO-1 mitigates HMP-induced liver recovery effects related to proliferation, in part, by downregulating the HGF-Akt axis

TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases

Tumor suppressor gene silencing through cytosine methylation contributes to cancer formation. Whether DNA demethylation enzymes counteract this oncogenic effect is unknown. Here, we show that TET1, a dioxygenase involved in cytosine demethylation, is downregulated in prostate and breast cancer tissues. TET1 depletion facilitates cell invasion, tumor growth, and cancer metastasis in prostate xenograft models and correlates with poor survival rates in breast cancer patients. Consistently, enforced expression of TET1 reduces cell invasion and breast xenograft tumor formation. Mechanistically, TET1 suppresses cell invasion through its dioxygenase and DNA binding activities. Furthermore, TET1 maintains the expression of tissue inhibitors of metalloproteinase (TIMP) family proteins 2 and 3 by inhibiting their DNA methylation. Concurrent low expression of TET1 and TIMP2 or TIMP3 correlates with advanced node status in clinical samples. Together, these results illustrate a mechanism by which TET1 suppresses tumor development and invasion partly through downregulation of critical gene methylation

Who are the users of a traditional Chinese sanfu acupoint herbal patching therapy in China? A cross-sectional survey

Sanfu acupoint herbal patching (SAHP) is a unique traditional Chinese medicine therapy, which has become popular for preventing acute attack of respiratory diseases such as asthma and chronic obstructive pulmonary disease, in many regions of mainland China. However, the knowledge about its users is lacking, especially the characteristics of the users and their experience and perspectives. To investigate the demographics of users, conditions for its use and the previous experience of SAHP, as well as users’ perspectives to provide baseline information for its practice. A cross-sectional consecutive-sample survey was conducted at outpatient departments from 3 traditional Chinese medicine hospitals in northern China. Each participant completed a questionnaire, after informed consent. Data description and analyses were done using SPSS 20.0. Among 949 SAHP users from 3 hospitals, female was predominant (n = 592; 62.4%), aged from 2 to 96 years (median = 52 years). 64.7% (380/587) of regular users have applied consecutively for 3 years or over, and the self-perceived satisfaction rates of respiratory diseases were from 45.9% to 77.7%. Positive attitude toward traditional Chinese medicine was the top reason for choosing SAHP. 42.4% of users held a motivation of being cured by SAHP and with great outcome expectancy on SAHP (70.8%). SAHP users were mainly female adults or elderly population; more than half were regular users, who predominantly used SAHP for various chronic respiratory diseases during their stable stage. The majority of users expressed satisfaction to previous SAHP for their respiratory diseases. 42.4% of users held a motivation of being cured by SAHP and with great outcome expectancy on SAHP (70.8%). The findings from this survey deserve further clinical trials for their clinical effectiveness.</br