长链非编码RNA的调控机制及其在原发性肝癌中的研究进展

长链非编码 RNA(long non-coding RNA,lncRNA)是近年来生命科学领域研究的热点,它是指一类转录本长度超过200 nt 的非蛋白编码序列。近年来的研究表明,lncRNA 具有基因调控的功能。某些 lncRNA 在肿瘤中的表达也是失调的,可以在转录前、转录、转录后及表观遗传学等多个层面发挥作用,本文就 lncRNA 生物学特点和调控机制及其在原发性肝癌中的研究进展作一综述。     

lncRNA在血管疾病中的作用机制研究进展

长链非编码RNA(lncRNA)是一类长度200个核苷酸的非编码RNA,他们可以在表观遗传、转录和翻译水平上调节基因的表达,并协调和整合多种信号通路参与细胞的分化、增殖、稳态和器官发育。研究表明,lncRNA可能通过调节血管平滑肌细胞、内皮细胞的增殖、迁移、凋亡等,从而对预防和减少血管系统疾病的发生起到作用。笔者就lncRNA与血管疾病关系及机制研究进展予以综述。     

长链非编码RNA在前列腺癌诊断中的研究进展

在人类30多亿个碱基对的基因序列中仅有不到2%的核酸序列用于编码蛋白,大部分基因不表达蛋白质,这一类基因称之为非编码RNA(non-coding RNA,ncRNA)。其中转录长度>200个核苷酸的RNA又被称为长链非编码RNA(long non-coding RNA,lncRNA)。大量基因研究表明,lncRNA的表达调控和突变与泌尿系统的肿瘤的发生密切相关。学者们通过研究其在PCa中的表达发现,lncRNA在PCa的发生、发展中起着重要的作用。本文结合国内外最新研究成果,将lncRNA在前列腺癌诊断中的研究进展作一综述。     

长链非编码RNA与前列腺癌

长链非编码RNA(lncRNA)是一类长度超过200个核苷酸,缺少特异开放阅读框,不具备蛋白质编码功能的RNA分子。近年来许多研究表明其可在表观遗传学、转录及转录后等多个水平参与基因的表达调控,影响细胞的生长发育、增殖、分化、代谢和凋亡等重要生理过程。lncRNA的异常表达与肿瘤的发生、发展、侵袭、转移及预后有着密切的联系。前列腺癌的发病是一个多因素、多步骤的复杂过程,而基因表达的异常在其中发挥着重要的作用。本文就lncRNA在前列腺癌中的作用及研究进展进行综述,为临床预防、诊断和治疗前列腺癌提供新策略。     

长链非编码RNA在胰腺癌转移中的研究进展

胰腺癌侵袭程度高,初诊即有局部淋巴结和远处转移。长链非编码RNA(IncRNA)最初被认为是基因转录组的"噪音"而未受到重视。但随着研究的深入,学者们发现lncRNA在人类基因组普遍被转录且起着重要的调控作用,与肿瘤的发生发展及转移密切相关。胰腺癌中有大量的lncRNA表达失调,其根据自身的亚细胞定位和结构不同,在胰腺癌转移中参与不同的生物学调控,涉及到上皮-间质转化(EMT),自噬,肿瘤代谢,关键驱动基因等多方面。研究lncRNA在肿瘤转移中的作用及其分子机制,有望为胰腺癌提供新的防治策略和新的治疗靶点。     

利用TCGA数据库构建男性乳腺癌的lncRNA-miRNA-mRNA ceRNA 网络

目的 通过构建男性乳腺癌的竞争性内源RNA(ceRNA)调控网络,探讨其发病机制.方法 从TCGA数据库(The Cancer Genome Atlas Database)中下载男性乳腺癌的长链非编码RNA(lncRNA)、微小RNA(miRNA)和mRNA的表达谱数据,通过R软件的limma数据包分析男性乳腺癌差异表...     

长链非编码RNA与肝癌

长链非编码RNA(lncRNA)是一类长度200 nt、不编码蛋白的RNA分子,可在表观遗传水平、转录和转录后水平调控基因的表达,从而广泛参与机体的生理与病理过程。越来越多的证据表明lncRNA参与肝细胞癌(肝癌)的发生与转移过程。研究表明,一部分异常表达的lncRNA与肝癌的发生、转移、进展有关。因此,lncRNA有望应用于肝癌的风险预测、诊断、治疗等。本文对近年来lncRNA在肝癌发病中的研究进展进行综述。     

甲状腺癌非编码RNA与mRNA差异表达谱及竞争性内源RNA调控网络分析

目的:通过生物信息学方法分析甲状腺癌预后相关的非编码RNA与mRNA及信号通路。方法:从癌症基因组图谱(TCGA)数据库中下载568例甲状腺癌患者的临床信息及其组织样本的非编码RNA(lncRNA、miRNA)与mRNA数据,筛选出差异表达的非编码RNA与mRNA,对差异表达的mRNA进行功能富集分析与通路分析;构建lncRNA-miRNA-mRNA的竞争性内源RNA(ceRNA)调控网络;结合临床信息进行生存分析获取与甲状腺癌预后相关的非编码RNA与mRNA。结果:共筛选出差异表达的lncRNA 497个(上调93个,下调404个),miRNA 72个(上调5个,下调67个),mRNA 1 097个(上调233个,下调864个)。功能富集分析结果显示差异表达的mRNA主要参与单组织过程、单组织细胞过程、刺激反应等生物学过程,受体结合、分子功能调节、钙离子调节等细胞功能以及细胞、细胞膜、细胞外组件等细胞构成过程。通路分析结果显示差异表达的mRNA主要参与神经反应受体-配体相互作用、细胞因子-细胞因子受体相互作用、肿瘤转录失调等信号通路的调节。构建的lncRNA-miRNA-mRNA ceRNA互作网络中,有2个差异表达lncRNA(MIR181A2HG、OPCML-IT1),1个差异表达miRNA(miRNA-184)和2个差异表达mRNA(E2F1、SALL3)与甲状腺癌的总体生存期明显有关(均P0.05)。结论:所筛选的非编码RNA与mRNA以及相关信号通路在甲状腺癌的预后密切相关,并为甲状腺癌发生、发展机制的研究提供了新的方向。     

长链非编码RNA及其与肿瘤相关研究进展

哺乳动物基因组中存在着大量非编码RNA是现代生物学研究的重大发现之一[1].应用基因芯片及全基因组和转录组测序技术研究证实编码蛋白质的RNA只占全部基因转录本的2％,剩余98％为非编码RNA[2]. 非编码RNA是指不编码蛋白质但在生物体生命活动中具有功能的RNA分子,按长度可将其分为短链非编码RNA和长链非编码RNA( long non-coding RNA,lncRNA)两大类.许多短链非编码RNA已被证实在肿瘤形成过程中发挥着重要作用[3],包括已被广泛研究并引起重视的microRNA和siRNA等.而后者指长度大于200个核苷酸的RNA,不参与或很少参与蛋白编码.目前研究已发现数十种lncRNA具有基因印记、计量补偿效应、RNA剪切等分子生物学作用,与肿瘤在内的多种疾病密切相关.本文将就lncRNA在肿瘤发生、发展中的作用做一综述.     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.