瞬时弹性扫描检测乙型肝炎后肝硬化病情严重程度的研究

目的 探讨瞬时弹性扫描(TE)诊断乙肝后肝硬化病情严重程度的临床价值.方法 对139例乙肝后肝硬化患者进行TE检测肝脏弹性值(LSM)、child-pugh分级和胃镜检查食管静脉曲张情况并进行统计分析.结果 肝脏弹性值与肝硬化child-pugh分级密切相关,Kendall相关系数为0.677(P=0.000).TE预测肝硬化child-pughB/C级、child-pughC级的受试者工作特征曲线下面积(AUROC)分别为0.906、0.934.LSM与食管静脉曲张分期的Kendall相关系数为0.357,TE预测食管静脉曲张和中度以上及重度食管静脉曲张的AUR0C分别0.779、0.717、0.694.结论 TE可较准确预测乙肝后肝硬化患者child-Pugh分级,对食管静脉曲张有中等程度的预测能力.     

肝脾硬度无创检测对慢性乙型肝炎肝硬化患者食管胃底静脉曲张的诊断价值研究

目的探讨肝脾硬度无创检测对慢性乙型肝炎肝硬化患者食管胃底静脉曲张的诊断价值。方法选取2018年1月～2019年1月我院收治的慢性乙型肝炎肝硬化患者50例为观察组,另选取同期于我院健康体检者50例为对照组,所有患者均经胃镜检查及肝、脾瞬时弹性成像技术检查,根据胃镜下食管胃底静脉曲张程度将观察组分为无、轻度、中度和重度曲张组。分析瞬时弹性成像检测出的肝、脾弹性值对慢性乙肝患者食管胃底静脉曲张的诊断价值。结果两组患者肝硬度值与脾硬度值均呈现正相关关系,经Pearson相关分析,P <0.05;随着食管胃底静脉曲张程度加重,患者肝、脾硬度值呈现增加趋势,组间相比,差异有统计学意义(P <0.05);受试者工作特性(ROC)曲线显示,肝、脾硬度值对肝硬化患者食管胃底静脉曲张诊断有较好效能,且脾脏硬度值的ROC曲线下面积(AUC)、灵敏度及特异度均显著高于肝脏硬度值。结论瞬时弹性成像技术检测肝脾硬度可为慢性乙型肝炎肝硬化患者食管胃底静脉曲张的诊断及预后预测提供可靠参考,临床应用价值较高。     

慢性乙型肝炎患者血CD4+CD25+调节性T细胞检测的临床意义

目的 探讨慢性乙型肝炎患者外周血CD4+CD25+调节性T细胞(CD4+ CD25+ Treg)检测的临床意义。方法 慢性HBV感染者48例（慢性HBV携带者10例为慢性HBV携带者组、慢性乙型肝炎18例慢性乙型肝炎组和乙肝肝硬化为乙肝肝硬化组20例）,以流式细胞仪检测血CD4+CD25+Treg细胞频率,实时荧光定量聚合酶链反应检测血HBV DNA载量。结果 血CD4+CD25+Treg细胞百分率：慢性HBV携带者组为(6.72±2.60)％、慢性乙型肝炎组为(8.56±3.12)％、乙肝肝硬化组为(11.59±4.34)％,组间差异有统计学意义（均P＜0.05）。血HBV DNA载量：慢性HBV携带者组为1.7 ×106拷贝/ml、慢性乙型肝炎组为4.3 ×105拷贝/ml、乙肝肝硬化组为6.8 ×104拷贝/ml,组间差异有统计学意义(P＜0.01);慢性肝病患者血CD4+CD25+调节性T细胞百分率与HBV DNA滴度正相关。结论 慢性肝病患者血Treg细胞频率与HBVDNA滴度正相关,提示Treg细胞在慢性乙型肝炎致病机制中起重要作用。     

彩色多普勒超声对门静脉高压患者食管静脉曲张的评估意义

目的:利用彩色多普勒超声检查并评估门静脉高压症患者静脉曲张的危险性,探讨其临床意义。方法:119例患者经临床确诊为肝硬化门静脉高压症,无食管静脉曲张30例,合并食管静脉曲张89例;轻度32例,中度41例,重度16例。分析彩超检查血流动力学参数的改变情况。结果:合并食管静脉曲张患者的门静脉血流速度、血流量与无食管静脉曲张患者比较,差异有统计学意义(P<0.05);重度静脉曲张的血流速度、血流量与轻度组相比,差异均有统计学意义(P<0.05)。结论:彩色多普勒超声能够便捷、准确提供血流信号参数,结合门静脉高压患者的其他临床资料,能够评价食管静脉曲张的严重程度,预测静脉曲张破裂出血并积极采取防治措施。     

肝脾硬度联合检测对肝硬化食管静脉曲张破裂出血的预测价值

目的 采用瞬时弹性成像技术检测肝硬度（LSM）、脾硬度（SSM）,探讨其对肝硬化患者食管静脉曲张破裂出血（EVB）的预测价值。方法 选择2016年7月至2017年12月在阜阳市第二人民医院就诊并行LSM、SSM检测的93例肝硬化患,分析LSM、SSM与肝硬化程度、食管静脉曲张（EV）程度及EVB的相关性,用受试者工作特征（ROC）曲线判断LSM、SSM对EVB的预测价值。结果 不同Child-Pugh分级肝硬化患者的LSM、SSM差异有统计学意义（P<0.05）,Child-Pugh分级越高,LSM和SSM越高;中-重度EV患者LSM、SSM高于无-轻度EV患者,差异有统计学意义（P<0.05）;EVB患者LSM、SSM高于无EVB患者,差异有统计学意义（P<0.05）。LSM、SSM判断EVB的最佳界值点为33.05、65.80 KPa,且SSM优于LSM,差异有统计学意义（P<0.05）。结论 LSM、SSM对EVB有较高的预测价值,且SSM优于LSM。     

血清谷氨酰转移酶水平与谷氨酰转移酶／ALT和AST／ALT比值联合分析对原发性肝癌的诊断价值研究

目的探讨血清谷氨酰转移酶（GGT）活性及GGT／ALT、AST／ALT比值联合分析对原发性肝癌的诊断价值。方法采用全自动生化分析仪对慢性乙型肝炎轻．中度140例、慢性乙型肝炎重度107例、慢性乙型重症肝炎97例、乙肝后肝硬化127例、HBsAg阳性的原发性肝癌139例患者进行GGT、AST、ALT检测,并分别将慢性乙型肝炎、乙肝后肝硬化、慢性乙型重症肝炎患者的统计结果与原发性肝癌患者进行比较分析。结果慢性乙型肝炎轻-中度、慢性乙型肝炎重度、慢性乙型重症肝炎存活组、慢性乙型重症肝炎死亡组、乙肝后肝硬化组、HBsAg阳性的原发性肝癌组GGT值分别为100．34±52．63,129．07±89．32,76．68±52．20,66．12±34．26,93．24±70．32,214．01±167．29,原发性肝癌组与其他各组相比,差异有统计学意义（P〈0．01）;各组AST/ALT比值分别为0．653±0．526、0．861±1．116、2．068±1．875、3．657±3．205、1．783±1．263、1．959±1．568,原发性肝癌组与慢性乙型肝炎轻-中度及重度组比较,差异有统计学意义（P〈0．01）;各组GGT／ALT比值分别为0．567±0．414、0．557±0．661、0．763±1．023、0．697±0．829、0．956±1．023、2．958±2．881,原发性肝癌组与其他各组比较,差异有统计学意义（P〈0．01）。结论在慢性乙型肝炎、乙肝后肝硬化患者,如果肝功能检查显示GGT升高,且AST／ALT〉1、GGT／ALT〉1,即表现为GGT〉ALT,且AST〉ALT时,应高度警惕原发性肝癌的存在,应进一步查甲胎蛋白、肝脏B超或肝脏CT,以争取对原发性肝癌作出早期诊断。     

水飞蓟宾对乙型肝炎肝硬化患者纤维化指标及FibroScan值的影响

目的 观察水飞蓟宾对乙型肝炎肝硬化患者纤维化指标的影响,并探讨FibroScan在此类患者中的应用价值.方法 将乙型肝炎肝硬化患者96例随机分为2组.对照组47例予恩替卡韦抗病毒治疗;治疗组49例在对照组用药基础上给予水飞蓟宾70mg口服,每天3次,连服半年.对比2组治疗前后血清透明质酸(HA)、Ⅲ型前胶原(PC-Ⅲ)、Ⅳ型胶原(Ⅳ-C)水平及FibroScan值变化.结果 治疗组治疗后血清PC-Ⅲ、HA、Ⅳ-C显著降低(P<0 05),FibroScan值明显降低(P<0.05);治疗后PC-Ⅲ、HA、Ⅳ-C及FibroScan值均低于对照组,差异均有统计学意义(P<0.05).结论 水飞蓟宾具有阻止肝纤维化的作用,FibroScan对肝功能衰竭患者的病情评价有较高价值.     

CT测脾静脉宽度与食管静脉曲张程度的关系

目的 探讨CT测脾静脉宽度与肝硬化患者食管静脉曲张程度之间的关系.方法 对我院2006年5月-2010年9月收治的61例肝硬化患者首先行胃镜检查,了解食管静脉曲张程度,根据患者食管静脉曲张程度分为3组,分别为I度、Ⅱ度、Ⅲ度食管静脉曲张组,随后采用螺旋CT进行上腹部三期扫描后,测量脾静脉宽度,对3组进行比较.结果 I度、Ⅱ度、Ⅲ度食管静脉曲张组脾静脉宽度分别为（1.05±0.12）、（1.82±0.23）、（2.02±0.28）cm,3组之间脾静脉宽度比较差异有统计学意义（P＜0.05）,Ⅲ度组脾静脉宽度高于I、Ⅱ度组脾静脉宽度（P＜0.05）,Ⅱ度组脾静脉宽度高于I度组脾静脉宽度（P＜0.01）.结论 脾静脉宽度可反映肝硬化患者食管静脉曲张程度,因此间接反映门静脉压力高低.     

508例肝硬化消化道出血危险因素分析

目的探讨肝硬化并发食管静脉曲张破裂出血的危险因素。方法回顾性分析508例肝硬化食管静脉曲张破裂出血患者的临床资料,并与同期住院的肝硬化食管静脉曲张未出血的184例患者资料进行比较,分析肝硬化消化道出血的危险因素。结果出血组凝血酶原时间、纤维蛋白原、国际标准化比率（INR）及门脉直径分别为（21.53±4.4）s、（1.12±0.57）g/L、1.67±0.60和（1.51±0.38）cm,和未出血组比较,差异有统计学意义。结果还显示出血组患者食管静脉曲张的Grade分级、曲张的范围、肝功能Child分级大于未出血组,差异有统计学意义。结论食管静脉曲张的程度高、肝功能分级差、凝血酶原时间、纤维蛋白原及INR异常是肝硬化消化道出血的高危因素。     

肝硬化腹水患者血清-腹水白蛋白梯度与食管静脉曲张破裂出血及肝功能分级的关系

目的总结分析肝硬化腹水患者的血清-腹水白蛋白梯度与食管静脉曲张破裂出血、肝功能分级间的关系。方法选择2012年1月至2013年12月我院收治的60例肝硬化腹水患者为研究对象,根据出血观察结果将患者分为出血组32例和非出血组28例,分别测定两组患者SAAG及肝功能指标。结果根据SAAG水平将60例患者分为三组,SAAG水平越高组患者试管静脉曲张比例、出血比例、Child分级C级比例越高,组间差异具有统计学意义(P<0.05)。结论肝硬化腹水患者SAAG水平越高,食管静脉曲张破裂出血概率越大,肝功能分级评分越高。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.