Novel miR-490-3p/hnRNPA1-b/PKM2 axis mediates the Warburg effect and proliferation of colon cancer cells via the PI3K/AKT pathway

BACKGROUND Heterogeneous ribonucleoprotein A1(hnRNPA1)has been reported to enhance the Warburg effect and promote colon cancer(CC)cell proliferation,but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been elucidated.AIM To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT pathway.METHODS Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b.The relationship between the expression values and the clinicopathological features of the patients was investigated.Differences in mRNA expression were analyzed using quantitative real-time polymerase chain reaction,while differences in protein expression were analyzed using western blot.Cell proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2’-deoxyuridine assays,and cell cycle and apoptosis were detected using flow cytometric assays.The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay.The Warburg effect was evaluated by glucose uptake and lactic acid production assays.RESULTS The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls(P<0.05).Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC,including stage I,II-III,and IV.Furthermore,the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification.HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway,thereby promoting proliferation of HCT116 and SW620 cells.However,the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b,effectively blocking the Warburg effect.CONCLUSION These findings suggest that the novel miR-490-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.

Preliminary study on the protective effect of electroacupuncture Neiguan acupoint pretreatment on rats with myocardial ischemia-reperfusion injury:role of the miR-214-3p/NCX1 axis

Background:Ischemia-reperfusion can worsen myocardial damage and increase the risk of death.Studies have revealed that ischemic preconditioning provides the best endogenous protection against myocardial ischemia-reperfusion injury(MIRI),and the principle of electroacupuncture(EA)preconditioning is comparable to that of myocardial ischemic preconditioning adaption.Our earlier research demonstrated that EA pretreatment inhibits the expression of calmodulin-dependent protein kinase IIδ(CaMKIIδ),sodium/calcium exchanger 1(NCX1),and cyclophilin D,hence providing protection against MIRI.However,the exact mechanism is still unknown.The expression of NCX1 mRNA is directly regulated by microRNA-214(miR-214).Moreover,it suppresses the levels of CaMKIIδand cyclophilin D.Whether these variables contribute to EA preconditioning to improve MIRI needs to be investigated,though.This study aimed to preliminarily determine whether EA pretreatment ameliorates MIRI by modulating the miR-214-3p/NCX1 axis.Methods:We used a rat MIRI model to investigate the effect of EA pretreatment on MIRI and the expression of miR-214-3p.In addition,adenovirus injection inhibited miR-214-3p expression in the rat MIRI model,and the influence of EA pretreatment towards MIRI was observed in the context of blocked miR-214-3p expression.Both the myocardial histological abnormalities and the alterations in the ST segment of the rat electrocardiogram were analyzed.NCX1 mRNA,cyclophilin D,and CaMKIIδexpression levels were also analyzed.Results:EA pretreatment improved MIRI.In rats with MIRI,EA administration increased miR-214-3p expression while decreasing NCX1 mRNA,cyclophilin D,and CaMKIIδproteins in cardiac tissues.The beneficial effect of EA pretreatment against MIRI was reversed,coupled with elevated levels of NCX1 mRNA,cyclophilin D,and CaMKIIδprotein expression,when an adenovirus injection disrupted the expression of miR-214-3p.Conclusions:Our findings preliminarily show that EA pretreatment inhibits the expression of NCX1 mRNA,cyclophilin D,and CaMKIIδproteins via miR-214-3p,hence exerting MIRI protection.

Environmental Impact Assessment Follow-Up of Seismic Survey Offshore Activities in Brazil

Follow-up of environmental impacts is an integral part of the Environmental Impact Assessment (EIA) process, closely related to the effectiveness of the instrument. EIA follow-up has been receiving a lot of interest from scientists and practitioners, though it is recognized as one of the weakest points of EIA systems globally. Also, EIA follow-up is influenced by the context, mainly in terms of the types of projects or activities and their related impacts on the environment. Therefore, the present paper is focused on the investigation of the follow-up stage applied to the activity of seismic survey coupled with offshore oil & gas exploitation in Brazil. Research was based on a qualitative approach that included document analysis and semi-structured interviews with analysts involved in EIA processes, and sought to generate evidence of effectiveness of the EIA follow-up as conducted by the Federal Environment Agency (Ibama) in order to situate the practice of follow-up in the broader context of international best practice principles. Based on the findings, it was concluded that, due to the peculiarities of offshore seismic survey, it is necessary to promote adaptations in the procedures for monitoring impacts in order to ensure proper alignment with the principles and conceptual foundations that guide EIA practice. Specifically, the timing of the execution of the activity imposes challenges for its integration into the “conventional” cycle that has guided the monitoring of the impacts in the EIA of projects.

表面效应对热-机多孔悬臂纳米梁力学性能的影响

表面效应对纳米结构的力学性能有重要影响。飞机上很多微纳尺度的结构可简化为悬臂梁。本工作分析表面效应对随从载荷作用下梯度多孔材料纳米悬臂梁在高温环境下非线性力学响应的影响。基于GurtinMurdoch表面弹性理论和非线性梁理论,建立梯度多孔材料梁在随从载荷以及温度场中的非线性控制微分方程。假定梯度多孔材料的性能在整个厚度范围内连续变化,且沿厚度呈两种余弦形式的非均匀孔隙率分布模式。采用打靶法求解梯度多孔材料悬臂纳米梁在热-随从载荷下的非线性力学响应。获得各种孔隙率系数和不同非均匀升温下悬臂纳米梁非线性力学响应的数值解,详细讨论材料表面弹性常数和表面应力对纳米悬臂梁力学响应的影响。结果表明:不同孔隙率系数和不同非均匀升温下梁的力学行为是不同的;纳米梁表现出十分显著的表面效应。

易地搬迁后续扶持政策效果评价与影响因素--基于西部10省1297户的实地调查数据

易地搬迁后续扶持工作既是助力搬迁群众稳定增收、加速社会融合、化解致贫返贫风险的关键,更是巩固拓展脱贫攻坚成果同乡村振兴有效衔接、推进实现共同富裕的核心要义。基于西部10省1297户农户的微观调查数据,采用主成分分析法和工具变量分位数回归模型,综合评估后续扶持政策成效并进行区域优先序评价,进而剖析后续扶持政策效果的影响因素,并立足情景化的个体生存状态,从多维视角探寻政策实施效果的异质性及其成因。研究发现:第一,后续扶持政策效益存在显著地区差异,大致呈现“西北高西南低”的空间分布特征;第二,非农生计、社会资本和内生动力是政策效果得以跃升的关键;第三,进一步讨论得知,农户收入层级与政策效益呈正相关关系,且安置区类型、社会资本差异和性别差异均会影响后续扶持政策效益的稳定性。为此,各地后续扶持工作应完善升级安置区配套基础和公共服务设施;多管齐下加快发展主导产业,加快推进群众经济社会融入步伐;激活群众自我发展内生动力;出台和优化差异化的后续扶持政策,增加搬迁群众的主观福利。

听觉-言语认知负荷下工作记忆容量对跟车行驶影响

听觉-言语认知负荷作为一种典型的认知负荷,是驾驶人认知分心的主要来源,容易导致驾驶绩效下降,认知负荷对驾驶绩效的影响程度与个体工作记忆有关。为研究听觉-言语认知负荷下工作记忆容量对跟车驾驶绩效的影响,本文开展心理学与模拟驾驶实验。首先,设置不同听觉-言语认知负荷水平的n-back任务,构建车头时距变化和前车速度变化的跟车场景;其次,采集并预处理工作记忆容量、驾驶人操作行为与车辆运行状态数据,选择跟车速度差、绝对加速度、横向稳定性、制动反应时间及跟车间距作为分析指标,获得36名被试数据;最后,采用方差分析及事后比较,分析认知负荷和工作记忆容量在跟车时对驾驶绩效的影响,并探讨两种因素对驾驶绩效的交互和调节作用。研究表明:认知负荷增加导致驾驶人更大的加减速倾向,更长的制动反应时间;工作记忆容量较高的驾驶人具有更小的制动反应时间和更稳定的跟车间距,更频繁的方向修正和更好的车道保持水平;在工作记忆容量和制动反应时间中,听觉-言语认知负荷具有正向调节作用。本文可以为驾驶安全培训干预提供驾驶人认知特性方面的见解和理论参考。

Effect of Hypertonic Versus Isotonic Saline Resuscitation on Heme Oxygenase-1 Expression in Visceral Organs Following Hemorrhagic Shock in Rats

To compare the early effects of hypertonic and isotonic saline resuscitation on heme oxygenase-1 （HO-1） expression in organs of rats with hemorrhagic shock. Rats were randomly divided into hypertonic saline resuscitation （HTS）, normal saline resuscitation （NS） and sham groups. HO-1 mRNA, protein expression and apoptosis were evaluated in organs. In the HTS group, significant difference was noted in HO-1 protein in small intestinal mucosa and liver compared with the NS and sham groups, and in HO-1 mRNA in liver and kidney compared with the sham group. The apoptosis of small intestinal mucosa, liver, heart, and lung was significantly lower in the HTS group than that in the NS group. In this study, small volume resuscitation with HTS can efficiently up-regulate the expression level of HO-1 in small intestinal mucosa and liver, which may be one of the mechanisms alleviating organ damage.

Age-at-injury effects of microglial activation following traumatic brain injury： implications for treatment strategies

Traumatic brain injury（TBI）remains one of the leading causes of disability and death in infants and children.Studies have demonstrated that the youngest age group（especially≤4 years old）exhibit worse functional outcome following moderate to severe TBI compared to older children or adults（Anderson et al.,2005;Emami et al.,2017）.These data suggest that age-at-injury may be an important determinant of outcome,

Effectiveness of MRA on embolized intracranial aneurysms: a comparison of DSA, CE-MRA, and TOF-MRA

Purpose: The endovascular treatment of intracranial aneurysms was proven safe and effective compared to the alternative method of surgical clipping, despite the high recurrence rate. Follow-up of embolized intracranial aneurysms is mandatory for the early detection of recurrence and improved outcomes. DSA is used as the reference standard for this assessment. To determine the effectiveness of MRA in follow-up evaluations of intracranial aneurysms after embolization by comparing DSA, CE-MRA, and TOF-MRA. Materials and Methods: Sixty-eight consecutive patients undergoing DSA, TOF-MRA, and CE-MRA during an interval of <1 week were enrolled in this 6-month study. Images were evaluated for occlusion status, patency of the parent vessels, and artifacts. The modified Raymond-Roy occlusion classification and Aneurysm Embolization Grades were used to assess the occlusion status and initial DSA images for detection of recurrence in two filtered study phases with optimized selection criteria. Seventeen observers(phase I: 9, phase II: 8) independently interpreted the double-blinded images. Agreement was expressed with a Fleiss kappa value; p < 0.05 was considered significant. Results: This study included 68 patients with 77 aneurysms; 38(49.35%) were treated with coil alone and 39(50.65%) with stent-assisted coiling. In both phases, DSA was superior to TOF-MRA and CE-MRA using MRRC(Phase I: k = 0.567, p ≤ 0.001; k = 0.287, p ≤ 0.001; k = 0.117, p ≤ 0.001, respectively; Phase II: k = 0.503, p ≤ 0.001; k = 0.303, p ≤ 0.001; k = 0.115, p = 0.038, respectively). TOF-MRA was as effective as DSA(TOF: k = 0.335, p ≤ 0.001; DSA: k = 0.323, p ≤ 0.001) for recurrence detection. Conclusion: We suggest TOF-MRA as a first-line follow-up tool to detect aneurysm recurrence, and DSA to quantify the filling space to make a definite decision on re-embolization.

Time and Dose-related Effects of the Pyrethroid Fluvalinate on Haemolymph Carbohydrates and Gut Lipids of Honeybees,Following in vivo Injection of very Low Doses

The injection to emerging adult workerbees with fluvalinate doses ranging from 1 femtomol to 1 nanomol per individual resulted in a reduction of haemolymph carbohydrate concentrations, particularly at the lowest dose 1 hour after injections. At the same time, a large increase was observed for triacylglycerols and to a much lesser extent for steroids and phospholipids with 0.1 picomol per bee. By contrast, fatty acids, steroids and triacylglycerols exhibited a depress at the higher dose. Most responses were thus biphasic, showing that much attention should be paid to the effects of very low doses of pesticide.

Effects of natural cerebrolysin on protective proteins and pro-apoptotic molecules in mesenchymal stem cells following beta-amyloid peptide1-40-induced endoplasmic reticulum stress

BACKGROUND： Studies have demonstrated that β-amyloid peptide （Aβ）, a characteristic pathological product of Alzheimer＇s disease （AD）, results in neuronal endoplasmic reticulum stress （ERS）. However, the mechanisms of traditional Chinese medicine against ERS in AD are poorly understood. OBJECTIVE： To measure expression levels of protective proteins （GRP78 and GRP94） of ER molecular partners and pro-apoptotic Caspase-12 ER membrane expression following application of traditional Chinese medicine natural cerebrolysin （NC） to treat Aβ1-40-induced ERS. DESIGN, TIME AND SETTING： A parallel-controlled study was performed at the Institute of Integrated Western and Traditional Chinese Medicine, Shenzhen Hospital of Southern Medical University between September 2006 and November 2008. MATERIALS： Sprague Dawley male rats, 6-8 weeks old, were used to harvest tibial and femoral bone marrow. Isolation and purification of mesenchymal stem cells （MSCs） were established from the whole bone marrow by removing non-adherent cells in primary and passage cultures. Aβ1-40 was provided by Sigma, USA. NC was provided by Shenzhen Institute of Integrated Chinese and Western Medicine, China. NC was predominantly composed of Renshen （Radix Ginseng）, Tianma （Rhizoma Gastrodiae）, and Yinxingye （Ginkgo Leaf） in a proportion of 1 ： 2： 2. Following conventional water extraction technology, an extract （1 ： 20） was prepared. Six adult, male, New Zealand rabbits underwent intragastric administration of NC extract （0.976 g/kg per day） for 1 month to prepare NC-positive serum, and the remaining 6 rabbits received intragastric administration of physiological saline to prepare normal blank serum. METHODS： A total of 500 nmol/L Aβ1-40 was used to establish ERS models of primary cultured MSCs. AD cell models were incubated with different doses of NC-positive serum （2.5%, 5%, and 10%）. MSCs treated with normal blank serum served as normal blank controls. MAIN OUTCOME MEASURES： Reverse transcription-polymerase chain reaction and fluorescent immunocytochemistry were respectively used to measure mRNA and protein expression levels of GRP78, GRP94, and Caspase-12 in MSCs. RESULTS： Following Aβ1-40 exposure, mRNA and protein expression levels of GRP78 and GRP94, as well as Caspase-12, significantly increased （P 〈 0.05）, suggesting successful establishment of ERS models. Following NC-positive serum application, mRNA and protein expression levels of GRP78 and GRP94 in MSCs significantly increased （P 〈 0.05 or P 〈 0.01）. However, mRNA and protein expression levels of Caspase-12 significantly decreased （P 〈 0.05, or P 〈 0.01） compared with the ERS model group. These effects were dose-dependent. CONCLUSION： NC downregulated Caspase-12 expression and upregulated GRP78 and GRP94 expression in MSCs in a dose-dependent manner under the state of Aβ1-40-induced ERS.

Improved Car-Following Model Considering Modified Backward Optimal Velocity and Velocity Difference with Backward-Looking Effect

In this paper, a new traffic flow model called the forward-backward velocity difference (FBVD) model based on the full velocity difference model is proposed to investigate the backward-looking effect by applying a modified backward optimal velocity using generalized backward maximum speed. The FBVD model belongs to the family of microscopic models that consider spatiotemporally continuous formulations. Neutral stability conditions of the discrete car-following model are derived using the linear stability theory. The stability analysis results prove that the modified backward optimal velocity has a significant positive effect in stabilizing the traffic flow. Through nonlinear analysis, a kink-antikink solution is derived from the modified Korteweg-de Vries equation of the FBVD model to explain traffic congestion of the model. The validity of this theoretical model is checked using numerical results, according to which traffic jams were found to have been significantly diminished by the introduction of the modified backward optimal velocity.

Anomalous spin Josephson effect in spin superconductors

The spin superconductor state is the spin-polarized triplet exciton condensate,which can be viewed as a counterpart of the charge superconductor state.As an analogy of the charge Josephson effect,the spin Josephson effect can be generated in the spin superconductor/normal metal/spin superconductor junctions.Here we study the spin supercurrent in the Josephson junctions consisting of two spin superconductors with noncollinear spin polarizations.For the Josephson junctions with out-of-plane spin polarizations,the possibleπ-state spin supercurrent appears due to the Fermi momentum-splitting Andreev-like reflections at the normal metal/spin superconductor interfaces.For the Josephson junctions with in-plane spin polarizations,the anomalous spin supercurrent appears and is driven by the misorientation angle of the in-plane polarizations.The symmetry analysis shows that the appearance of the anomalous spin Josephson current is possible when the combined symmetry of the spin rotation and the time reversal is broken.

Effect of calcitonin gene-related peptide and nerve growth factor on spatial learning and memory abilities of rats following focal cerebral ischemia/reperfusion

BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them on relieving learning and memory injury following cerebral ischemia/reperfusion should be further studied. OBJECTIVE: To study the effects of exogenous CGRP and NGF on learning and memory abilities of rats with focal cerebral ischemia/reperfusion. DESIGN: Randomized controlled animal study. SETTING: Department of Neurosurgery, the Second Hospital of Xiamen; Department of Neurosurgery, the Second Affiliated Hospital of China Medical University; Department of Neurobiology, Basic Medical College of China Medical University. MATERIALS: A total of 30 healthy male SD rats, aged 8 weeks, of clean grade, weighing 250-300 g, were provided by Experimental Animal Department of China Medical University. All rats were randomly divided into sham-operation group, ischemia/reperfusion group and treatment group with 10 in each group. The main reagents were detailed as the follows: 100 g/L chloral hydrate, 0.5 mL CGRP (2 mg/L, Sigma Company, USA), and NGF (1× 106 U/L, 0.5 mL, Siweite Company, Dalian). METHODS: The experiment was carried out in the Department of Neurobiology, Basic Medical College of China Medical University from February to July 2005. Rat models of middle cerebral artery occlusion were established by method of occlusion, 2 hours after that rats were anesthetized and the thread was slightly drawn out for 10 mm under direct staring to perform reperfusion. Rats in the ischemia/reperfusion group received intraperitoneal injection of 1 mL saline via the abdomen at two hours later, while rats in the treatment group at 2 hours later received intraperitoneal injection of 2 mg/L CGRP (0.5 mL) and 1×106 U/L NGF (0.5 mL) once a day for 10 successive days. First administration was accomplished within 15 minutes after ischemia/reperfusion. Rats in the sham-operation group were separated of the vessels without occlusion or administration. The neural function was evaluated with Zea Longa 5-grade scale. Animals with the score of one, two and three points received Morris water-maze test to measure searching time on platform (omitting platform-escaping latency). Meanwhile, leaning and memory abilities of animals were reflected through testing times of passing through platform per minute. MAIN OUTCOME MEASURES: Experimental results of omitting platform-escaping latency and spatial probe. RESULTS: Three and two rats in the ischemia/reperfusion group and treatment group respectively were not in accordance with the criteria in the process, and the rest were involved in the final analysis. ① Comparisons of platform-escaping latency during Morris water-maze test in all the three groups: Ten days after modeling, the platform-escaping latency in the ischemia/reperfusion group was obviously longer than that in sham-operation group (P < 0.01), and was significantly shorter than that in the treatment group (P < 0.01). ② Comparisons of times of passing through platform in all the three groups: Times of passing through platform were remarkably less in the ischemia/reperfusion group than those in the sham-operation group [(1.79±0.39), (4.30±0.73) times/minute, P < 0.01], and those were markedly more in the treatment group than the ischemia/reperfusion group [(3.16±1.03), (1.79±0.39) times/minute, P < 0.01]. CONCLUSION: CGRP and NGF are capable of ameliorating the abilities of spatial learning and memory in MCAO rats, which indicates that CGRP and NGF can protect ischemic neurons.

Effect of long-term low dose of aspirin on severity of disease following onset of acute cerebral infarction

BACKGROUND： Aspirin can decrease the incidence risk of high-risk crowdgroup of cerebral infarction, but there are still controversy if it might decrease the degree of disease in degree of patients with acute cerebral infarction. OBJECTIVE： To observe the effect of lower dose of aspirin during taking for a long time on disease degree of disease following onset of acute cerebral infarction. DESIGN： Grouping according to the admission time and 1：1 paired observation.SETTING ： Department of Neurology, Qilu Hospital of Shandong University.PARTICIPANTS ： The participants in present study were 321 patients with acute cerebral infarction who received treatments in the Department of Neurology, Qilu Hospital of Shandong University from January 1999 to June 2000. There were 190 male and 131 female ,with mean （65±11 ）years of age. Inclusive criteria： ① A focal neurological disturbance occurred suddenly and had lasted for more than 24 hours, patients were admitted within 3 days after onset of disease; ② A computed tomography of the brain was performed and excluded hemorrhage in all patients; ③ The patients were proved internal carotid occlusions by clinical features and image findings; ④ The functions of limbs were normal （before the first stroke） or almost normal （before the second stroke）. Exclusive criteria：①The patients who had have cardiogenic cerebral embolism; ②The patients who had taken warfarin orally and other platelet agglutination drugs. METHODS ：①All the patients were divided into 2 groups according to whether they had taken aspirin before： aspirin-treated group （n=110） and blank control group （n=211）. there were 70 male and 40 female in aspirin-treated group, with average（65±10） years of age.All patients had taken 50-100 mg/d aspirin for 6 months to 10 years before onset. There were 120 male and 91 female in blank control group, with average （65±13） years of age. Patients received a clinical scoring within 3 days and similar therapeutic measures （such as anti-platelet agglutination, improving cerebral circulation and metabolism-promoting reagent）. Two groups of patients had the same basic conditions except for taking aspirin or not before. ②The matched pairs were made between 50 cases selected from aspirin-treated group and 50 cases from non-aspirin-treated groups according to age, gender, and other stroke risk factors. ③ Evaluation： Degree of disease after onset was evaluated by means of Acute Cerebral Infarction Clinical Neurologic Impairment Degree Scoring Standard of Carotid Artery System. MAIN OUTCOME MEASURES： Acute Cerebral Infarction Clinical Neurologic Impairment Degree Scoring Standard of Carotid Artery System. RESULTS ： All 321 patients entered the stage of analysis with no loss in the midway. ① The symptom following onset of acute cerebral infarction was evaluated with clinical neurologic impairment scoring criteria, there were no significant differences between aspirin group and blank control group [（17.39±9.90） vs （16.22 ± 9.98） （t=1.025, P〉 0.05）]. ② No significant differences were found in 1：1 matched pairs of 100 cases from aspirin group and blank control group （t=1.74, P 〉 0.05）. CONCLUSION ： Taking a lower dose of aspirin during long time may not decrease the degree of disease following onset of acute cerebral infarction.

Effect of ketamine on aquaporin-4 expression and neuronal apoptosis in brain tissues following brain injury in rats

BACKGROUND： Aquaporin-4 （AQP-4） is closely related to the formation of brain edema. Neuronal apoptosis plays an important part in the conversion of swelled neuron following traumatic brain injury. At present, the studies on the protective effect of ketamine on brain have involved in its effect on aquaporin-4 expression and neuronal apoptosis in the brain tissues following brain injury in rats. OBJECTIVE： To observe the effect of ketamine on AQP-4 expression and neuronal apoptosis in the brain tissue following rat brain injury, and analyze the time-dependence of ketamine in the treatment of brain injury.DESIGN： Randomized grouping design, controlled animal tria SETTING ： Department of Anesthesiology, the Medical School Hospital of Qingdao University MATERIALS： Totally 150 rats of clean grade, aged 3 months, were involved and randomized into control group and ketamine-treated group, with 75 rats in each. Each group was divided into 5 subgroups separately at 6,12, 24, 48 and 72 hours after injury, with 15 rats at each time point. Main instruments and reagents： homemade beat machine, ketamine hydrochloride （Hengrui Pharmaceutical Factory, Jiangsu）, rabbit anti-rat AQP-4 polyclonal antibody, SABC immunohistochemical reagent kit and TUNEL reagent kit （Boster Co.,Ltd., Wuhan）. METHODS： This trial was carried out in the Institute of Cerebrovascular Disease, Medical College of Qingdao University during March 2005 to February 2006. A weight-dropping rat model of brain injury was created with Feeney method. The rats in the ketamine-treated group were intraperitoneally administered with 50 g/L ketamine （120 mg/kg） one hour after injury, but ketamine was replaced by normal saline in the control group. In each subgroup, the water content of cerebral hemisphere was measured in 5 rats chosen randomly. The left 10 rats in each subgroup were transcardiacally perfused with ketamine, then the brain tissue was made into paraffin sections and stained by haematoxylin and eosin. Neuronal morphology was observed. AQP-4 expression and neuronal apoptosis were measured with immunohistochemical method and TUNEL method respectively. MAIN OUTCOME MEASURES： Water content in brain tissue, neuronal morphology, the number of AQP-4 positive neurons and TUNEL positive neurons in rats of two groups at each time point after injury. RESULTS： Totally 150 rats entered the stage of result analysis. （1） Water content of brain tissue： The water content of brain tissue at each time point after injury in the ketamine-treated group was lower than that in the control group. There were very significant differences in water content at 12 and 24 hours after injury respectively between ketamine-treated group and control group [（77.34±2.35）% vs. （82.31 ±1.48）%; （78.01 ±2.21 ）% vs. （83.86±2.37）%, t=-4.001 6,4.036 7, both P 〈 0.01]. （2） Neuronal morphology： Pathological changes in traumatic region and peripheral region of injury in the ketamine-treated group were significantly lessened, and necrotic and apoptotic cells in the ketamine-treated group were also significantly reduced as compared with control group. （3） AQP-4 expression： AQP-4 positive neurons at each time point in the ketamine-treated group were significantly less than those in the control group. There were very significant differences in AQP-4 expression at 12 and 24 hours after injury between ketamine-treated group and control group [（34.17±4.74） /visual field vs. （43.42±5.65） /visual field;（40.83±3.17） /visual field vs. （58.88±6.23） /visual field,t=3.966 3,8.165 7, both P〈 0.01]. （4） Neuronal apoptosis： TUNEL positive neurons at each time point in the ketamine-treated group were less than those in the control group. There were very significant differences in the neuronal apoptosis at 12 and 24 hours after injury between ketamine-treated group and control group [（26.25±3.04） /visual field vs. （32.75±4.39） /visual field; （29.33± 4.02） /visual field vs. （39.83±5.61） /visual field,t=-3.849 3,5.169 2,both P 〈 0.01]. CONCLUSION： Ketamine can reduce brain edema, AQP-4 expression and neuronal apoptosis following brain injury in rats, and has obvious therapeutic effect on brain injury, especially at 12 and 24 hours after injury.

Yield Increasing and Quality Improving Effects of Smash-ridging Method("4453" Effects) and Its Potential in Benefiting the Nation and the People

Yuan Longping proposed that smash-ridging technology could be extend-ed widely nationwide. ln the research, smash-ridging technology reconstruct cultiva-tion layers with loose soils in agricultural fields, creating ＂4453＂ effects, as fol ows： ＂Four increases＂ include to increase loosen soil quantity in cultivation layers, soil nutri-ents use, ＂water pool＂ in soils, and ＂oxygen pool＂ in soils. Four reductions are to reduce soil erosion, carbon emission, salt content and heavy metal in soils. Five resistances refer to improve crop resistance capacity in terms of drought, high tem-perature, lower temperature, disease and lodging. Three improvements indicate to enhance photosynthetic efficiency over 10%, yield in 10%-30% and quality over 5%. lt is researched that without additional chemical fertilizer, yield could increase by 10% by labor force, animal, tractor or smash-ridging machine. What’s more, by smash-ridging cultivation, the depth can be 20 times or higher compared with tractor cultivation, with looser soils. lt is estimated that if smash-ridging cultivation is applied once in agricultural lands in China, present soil layers can be twice as deep as present. Specifical y, the thickness of loose soil-layers could be extended from 10-18 cm at present to 25-35 cm, and natural rainfal would increase by 40 bil ion cm3. After vitalization of soil nutrients, chemical fertilizer would decrease by 7 bil ion kg, and the increased c rops would feed more than 300 mil ion population as per yield at 7 50 kg/hm2.

Effect of switching from treatment with nucleos(t)ide analogs to pegylated interferon α-2a on virological and serological responses in chronic hepatitis B patients

AIM To investigate the efficacy of switching to pegylated interferon-α-2a(Peg IFNα-2a) treatment in nucleos(t)ide analog(NA)-treated chronic hepatitis B(CHB) responder patients. METHODS A 48-wk prospective and retrospective treatment trial of NA-treated CHB patients who had received entecavir(ETV) for at least 48 wk and had serum hepatitis B virus(HBV)-DNA < 500 IU/m L, serum hepatitis B envelope antigen(HBe Ag) < 100 S/CO, serum alanine aminotransferase, and aspartate aminotransferase levels < 2 × the upper limit of normal of 40 IU/L was performed. The effects on virological and serological responses and adverse reactions to 0.5 mg daily ETV for 48 wk vs switching to Peg IFNα-2a were compared. Forty-four patients were randomized to be switched from NA treatment to the Peg IFNα-2a group, and 44 patients were simultaneously randomized to the ETV group. RESULTS After 48 wk of therapy, the decrease in hepatitis B surface antigen(HBs Ag) levels was greater in the Peg IFNα-2a group than in the ETV group(3.1340 log10 IU/m L vs 3.6950 log10 IU/m L, P = 0.00). Seven patients who were anti-HBs-positive at baseline achieved HBs Ag loss when switched to Peg IFNα-2a(15.91% vs 0%,P = 0.018). The HBe Ag serological conversion rate was higher in the Peg IFNα-2a group than in the ETV group; however, the difference was not significant because of the small sample sizes(34.38% vs 21.88%, P = 0.232). In the Peg IFNα-2a group, patients with HBs Ag levels < 1500 IU/m L at baseline had higher HBe Ag seroconversion and HBs Ag loss rates at week 48 than those with HBs Ag levels ≥ 1500 IU/m L(HBe Ag seroconversion: 17.86% vs 62.5%, P = 0.007; HBs Ag loss: 41.67% vs 6.25%, P = 0.016). Moreover, patients with HBs Ag levels < 1500 IU/m L at week 24 had higher HBs Ag loss rates after therapy than those with HBs Ag levels ≥ 1500 IU/m L(36.84% vs 0%, P = 0.004). However, there were no statistically significant differences in HBe Ag seroconversion rates(47.06% vs 25.93%, P = 0.266). CONCLUSION NA-treated CHB patients switched to sequential Peg IFNα-2a achieved highly potent treatment termination safely.

Flow behavior in microchannel made of different materials with wall slip velocity and electro-viscous effects

In a microfluidic system, flow slip velocity on a solid wall can be the same order of magnitude as the average velocity in a microchannel. The flow-electricity interaction in a complex microfluidic system subjected to joint action of wall slip and electro-viscous effect is an important topic. This paper presents an analytic solution of pressuredriven liquid flow velocity and flow-induced electric field in a two-dimensional microchannel made of different materials with wall slip and electro-viscous effects. The Poisson- Boltzmann equation and the Navier-Stokes equation are solved for the analytic solutions. The analytic solutions agree well with the numerical solutions. It was found that the wall slip amplifies the fow-induced electric field and enhances the electro-viscous effect on flow. Thus the electro-viscous effect can be significant in a relatively wide microchannel with relatively large kh, the ratio of channel width to thickness of electric double layer, in comparison with the channel without wall slip.

Potential Toxicological and Cardiopulmonary Effects of PM2,5 Exposure and Related Mortality:Findings of Recent Studies Published during 2003-2013

Air pollution has environmental issue owing become a serious to its diverse harmful effects on the physical and biological environment. According to the Environmental Protection Agency （EPA） and the World Health Organization （WHO）, air pollution affects millions of people worldwide. Hundreds of thousands of deaths each year and a range of diseases, particularly among vulnerable groups （i.e., children, the elderly, and people with special medical conditions）, are attributed to air pollution. These effects are not always caused by single pollutant in the air; rather, they are considered consequences of the multi-pollutants to which people are simultaneously exposed.