The preventive and therapeutic effects of AAV1-KLF4-shRNA in cigarette smoke-induced pulmonary hypertension

We found previously that KLF4 expression was up-regulated in cultured rat and human pulmonary artery smooth muscle cells (PASMCs) exposed to cigarette smoke (CS) extract and in pulmonary artery from rats with pulmonary hypertension induced by CS. Here, we aim to investigate whether CS-induced pulmonary hypertension (PH) is prevented and ameliorated by targeted pulmonary vascular gene knockdown of KLF4 via adeno-associated virus 1 (AAV1)-KLF4-shRNA in vivo in rat model. The preventive and therapeutic effects were observed according to the different time-point of AAV1-KLF4-shRNA intratracheal administration. We tested haemodynamic measurements of systemic and pulmonary circulations and observed the degree of pulmonary vascular remodelling. In the preventive experiment, KLF4 expression and some pulmonary circulation hemodynamic measurements such as right ventricular systolic pressure (RVSP), mean right ventricular pressure (mRVP), peak RV pressure rate of rise (dP/dt max) and right ventricle (RV) contractility index were increased significantly in the CS-induced PH model. While in the prevention group (AAV1-KLF4-shRNA group), RVSP, mRVP, dP/dt max and RV contractility index which are associated with systolic function of right ventricle decreased and the degree of pulmonary vascular remodelling relieved. In the therapeutic experiment, we observed a similar trend. Our findings emphasize the feasibility of sustained pulmonary vascular KLF4 gene knockdown using intratracheal delivery of AAV1 in an animal model of cigarette smoke-induced PH and determined gene transfer of KLF4-shRNA could prevent and ameliorate the progression of PH.     

布鲁氏茵病防治基础研究现状与展望

布鲁氏菌病（简称布病）是由布鲁氏菌属细菌侵入机体引起的人畜共患传染病．近年来,布病疫情在世界范围内呈反弹趋势,我国尤甚．进入2000年以后,人间布病在我国成为报告发病数上升速度最快的传染病之一,令我国布病防治形势严峻．为了明确我国布病防治工作的现状和需求、最新研究现状和研究动态以及面临的挑战和机遇,深入研讨分析我国布病防治研究中的重大科学和关键技术问题,凝练和提出今后我国布病防治研究发展中亟需关注、解决的重要基础科学问题,在国家自然科学基金委员会资助下,由中国疾病预防控制中心地方病控制中心主办,哈尔滨医科大学、中国疾病预防控制中心传染病预防控制所和内蒙古地方病防治研究中心共同协办,于2013年6月21日召开了由来自全国布病防治与基础研究领域专家共同参加的“布鲁氏菌病防治基础研究发展战略研讨会”．会议在我国布病疫情最重的省份内蒙古自治区呼和浩特市召开,中国疾病预防控制中心传染病预防控制所、军事医学科学院疾病预防控制所、石河子大学、中国兽医药品监察所等19家从事布病防治与基础研究的科研院所、高等院校、疾病防治机构的40余位专家参加了此次会议．现结合文献资料以及本次会议的内容,对国内外布病流行现状、研究进展,以及影响我国布病防治的亟需解决的科学问题和建议作一综述．     

近年广西银杏病虫害发生及防治对策

近年来 ,银杏病虫害在广西各栽培地区普遍发生。主要报导了在广西危害比较严重 ,造成较大经济损失的病虫害及其危害症状、形态特征、发生规律和防治措施。这些病虫害在广西多属首次发现报导。     

潍坊市小儿腹泻状况分析

为了掌握潍坊市冬、秋季节婴幼儿腹泻的病因,在2008年10月1日~12月9日期间,对城内四所市级医疗机构的门诊和住院腹泻病人进行了统计,对住院腹泻病人采样作了检测,并对其进行分析。结果显示,潍坊市秋冬季腹泻患者主要由轮状病毒所引起,接种轮状病毒疫苗可有效预防轮状病毒腹泻。     

Helicobacter spp. Other Than Helicobacter pylori

Non- H. pylori Helicobacter species (NHPHS) are associated with several important human and animal diseases. In the past year research into this group of bacteria has continued to gain attention, and novel species have been described in new niches owing to improvements in detection methods. Polymerase chain reaction and/or sequencing remain the gold standard for the detection of this genus. New insights into the pathogenesis of the NHPHS in hepatobiliary, gastric, and intestinal diseases were gained. In particular, data revealed interaction between hepatic steatosis and infectious hepatitis in the development of hepatocellular carcinoma. Evidence of an association between hepatitis C virus and Helicobacter spp. in hepatocarcinoma development was also provided; and male sex hormone signaling appeared to influence infectious hepatitis induced by Helicobacter hepaticus . More findings support an association between Helicobacter heilmannii and gastric adenocarcinoma; and in mice, mucins MUC4 and MUC5 but not MUC1 influence the colonization and pathogenesis of Helicobacter felis . Data indicated that the roles of the adaptive immune system in H. hepaticus -induced intestinal tumorigenesis are different in the small and large intestines, and environmental factors, such as bile acids may modulate H. hepaticus carcinogenic potential. New reports in the prevention and eradication of NHPHS showed a protective response against Helicobacter suis induced by vaccine administration, and a successful cross-foster rederivation method successfully eradicated Helicobacter spp. from contaminated mice litters. Overall, the studies provided insights into the pathophysiology of Helicobacter species other than Helicobacter pylori.     

西藏年楚河流域水土流失及生态重建研究

西藏著名粮仓年楚河流域位于北纬 2 8°10′～2 9°2 0′、东经 88°35′～ 90°15′ ,地处喜马拉雅地质构造区中段。年楚河全长 2 17ｋｍ ,平均坡降 0 .6 1% ,落差达 132 2ｍ ,大致呈东南 西北流向 ,于日喀则附近逆向汇入雅鲁藏布江。行政区划上包括康马、日喀则县大部和江孜、白朗县全部 ,总面积 6 311ｋｍ2 ,耕地面积 4 .70× 10 4 ｈａ ,农业人口 16 .5 9万人 ,分别占西藏自治区的 0 .9% ,13.5 %和 7.7% ,现为国家级农业综合开发区“一江两河”(雅鲁藏布江中游及其支流拉萨河、年楚河流域 )地区的重要组成部分。近年 ,水土流失对生态环…     

Bear deterrence with scare devices,a non-lethal tool in the use-of-force continuum

Wild animals eating agricultural products and coming close to people's residences are primary causes of human–wildlife conflict worldwide. When carnivores eat anthropogenic foods and cause human safety concerns, it often results in the removal of the animals and public demand for reduced wildlife populations. The use of remote methods, such as scare devices, to deter carnivores has been touted in the literature; however, efficacy evidence remains thin. I test the efficacy of a widely available motion-activated solar alarm lamp to deter grizzly bears (Ursus arctos) from farms in Montana, USA. When scare devices were activated, there was a 46% reduction in the odds bears would access an attractant. For every additional scare device, there was an additional 44% reduction in the odds of a bear getting the food. Additionally, scare devices caused bears to be more vigilant and increase movement behavior. More bears in a group led to loss of deterrence efficacy, and there was no evidence for habituation to the aversive stimuli. This deterrence method was most effective in August and for fungicide-treated wheat. Out of 21 farms, scare devices stopped bears from returning to 11 sites. Overall, scare devices can be a cheap and easy first step to preventing, or resolving, some grizzly bear issues in the use-of-force continuum, which hierarchically organizes conflict responses from non-lethal to more severe.     

Lithium in drinking water and the incidences of crimes,suicides, and arrests related to drug addictions

Using data for 27 Texas counties from 1978-1987, it is shown that the incidence rates of suicide, homicide, and rape are significantly higher in counties whose drinking water supplies contain little or no lithium than in counties with water lithium levels ranging from 70-170 micrograms/L; the differences remain statistically significant (p less than 0.01) after corrections for population density. The corresponding associations with the incidence rates of robbery, burglary, and theft were statistically significant with p less than 0.05. These results suggest that lithium has moderating effects on suicidal and violent criminal behavior at levels that may be encountered in municipal water supplies. Comparisons of drinking water lithium levels, in the respective Texas counties, with the incidences of arrests for possession of opium, cocaine, and their derivatives (morphine, heroin, and codeine) from 1981-1986 also produced statistically significant inverse associations, whereas no significant or consistent associations were observed with the reported arrest rates for possession of marijuana, driving under the influence of alcohol, and drunkenness. These results suggest that lithium at low dosage levels has a generally beneficial effect on human behavior, which may be associated with the functions of lithium as a nutritionally-essential trace element. Subject to confirmation by controlled experiments with high-risk populations, increasing the human lithium intakes by supplementation, or the lithiation of drinking water is suggested as a possible means of crime, suicide, and drug-dependency reduction at the individual and community level.     

Cigarette smoke metabolically promotes cancer,via autophagy and premature aging in the host stromal microenvironment

Cigarette smoke has been directly implicated in the disease pathogenesis of a plethora of different human cancer subtypes, including breast cancers. The prevailing view is that cigarette smoke acts as a mutagen and DNA damaging agent in normal epithelial cells, driving tumor initiation. However, its potential negative metabolic effects on the normal stromal microenvironment have been largely ignored. Here, we propose a new mechanism by which carcinogen-rich cigarette smoke may promote cancer growth, by metabolically “fertilizing” the host microenvironment. More specifically, we show that cigarette smoke exposure is indeed sufficient to drive the onset of the cancer-associated fibroblast phenotype via the induction of DNA damage, autophagy and mitophagy in the tumor stroma. In turn, cigarette smoke exposure induces premature aging and mitochondrial dysfunction in stromal fibroblasts, leading to the secretion of high-energy mitochondrial fuels, such as L-lactate and ketone bodies. Hence, cigarette smoke induces catabolism in the local microenvironment, directly fueling oxidative mitochondrial metabolism (OXPHOS) in neighboring epithelial cancer cells, actively promoting anabolic tumor growth. Remarkably, these autophagic-senescent fibroblasts increased breast cancer tumor growth in vivo by up to 4-fold. Importantly, we show that cigarette smoke-induced metabolic reprogramming of the fibroblastic stroma occurs independently of tumor neo-angiogenesis. We discuss the possible implications of our current findings for the prevention of aging-associated human diseases and, especially, common epithelial cancers, as we show that cigarette smoke can systemically accelerate aging in the host microenvironment. Finally, our current findings are consistent with the idea that cigarette smoke induces the “reverse Warburg effect,” thereby fueling “two-compartment tumor metabolism” and oxidative mitochondrial metabolism in epithelial cancer cells.