射血分数降低的心力衰竭患者的中西药治疗研究进展

心力衰竭（HF）按照左心室射血分数（LVEF）的高低分为射血分数降低的心力衰竭（HFrEF）、射血分数保留的心力衰竭（HFpEF）及射血分数中间值的心力衰竭（HFmrEF）。HFrEF是HF的主要类型,发病率逐年升高。临床现有的治疗HFrEF的传统药物虽经联合用药,可以在一定程度上延缓病程及改善患者症状及预后,但传统药物不良反应较多,对HFrEF的治疗效果有限,且HFrEF的合并症或并发症得不到有效治疗,患者的再住院率及死亡率仍较高。近来随着对HFrEF发生发展及药物作用机制的进一步研究探索,开发出了多种中西药弥补传统药物治疗HFrEF时的不足。本文就治疗HFrEF的中西药典型代表药物伊伐布雷定、沙库巴曲缬沙坦、阿利吉仑、麝香保心丸、芪苈强心胶囊的药理作用特点及其治疗研究进展进行综述。     

不同左室射血分数的心力衰竭患者临床特征比较

目的 比较左室射血分数（LVEF）减低的心力衰竭与LVEF中间范围的心力衰竭临床特征的不同,为不同LVEF心力衰竭的诊疗提供依据。方法 选择2016年5月至2017年5月安徽省立医院心内科住院的346例LVEF低于正常值的心力衰竭患者,分为LVEF减低的心力衰竭（HFrEF）组、LVEF中间范围的心力衰竭（HFmrEF））组,比较两组患者的一般资料、合并症、心力衰竭的病因、辅助检查结果。结果 HFrEF组患者的年龄、体质指数、心率、男性患者比例均高于HFmrEF组,但吸烟比例低于HFmrEF组,差异有统计学意义（P<0.05）。HFmrEF组患者合并高血压病、糖尿病、脑卒中的比例较高,与HFrEF组相比,差异有统计学意义（P<0.05）。HFrEF组缺血性心肌病、高血压性心脏病患者比例低于HFmrEF组,扩张型心肌病患者比例高于HFmrEF组,差异有统计学意义（P<0.05）。与HFmrEF组比较,HFrEF组左室舒张末径更大,谷丙转氨酶、谷草转氨酶更高,但室间隔肥厚患者比例较低,差异均有统计学意义（P<0.05）。结论 不同LVEF心力衰竭患者的多项临床特征存在明显差异。     

伊伐布雷定在慢性射血分数降低心力衰竭易损期的运用及再入院影响因素分析#br#

摘要：目的　探讨伊伐布雷定（Iva）在慢性射血分数降低心力衰竭（HFrEF）易损期的运用及易损期再入院的影响因素。方法　根据是否服用Iva把402例易损期慢性HFrEF患者分为对照组（142例）和观察组（260例）。对照组依据指南给与抗心力衰竭治疗,观察组在对照组的基础上给与Iva。对比2组的疗效、心脏不良事件、心功能指标、炎性因子。采用Logistic回归分析易损期慢性HFrEF患者再入院的影响因素。结果　观察组的疗效明显好于对照组,再住院比例明显低于对照组（P＜0.05）。治疗后与对照组相比,观察组的24 h平均心率减慢,左心室射血分数（LVEF）增高,左心室舒张末期内径（LVEDD）减小,6 min步行距离（6MWD）延长,N末端B型利钠肽原（NT-proBNP）、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6和超敏C-反应蛋白（hs-CRP）水平均降低（P＜0.05或P＜0.01）。Logistic回归分析结果显示不按时服药、独居是易损期慢性HFrEF患者再入院独立危险因素,而每周复诊1次则是独立保护因素。结论　Iva可提高易损期慢性HFrEF的疗效,降低易损期再入院率和炎性因子水平,同时可改善心功能指标。不按时服药和独居的慢性HFrEF患者在易损期更容易再入院,而每周复诊1次则可降低再入院率。     

衰弱对老年女性慢性射血分数保留型心力衰竭患者预后的影响

目的探讨衰弱对老年女性慢性射血分数保留型心力衰竭(HFpEF)患者预后的影响。方法选取2017年1月至2019年1月在华中科技大学同济医学院附属梨园医院诊治的老年女性慢性HFpEF患者。选择合并衰弱的70例患者为衰弱组;按照1∶2比例选择年龄、体重指数和左心室射血分数匹配的未合并衰弱的140例患者为对照组。随访12个月,记录主要不良心血管事件(MACE)发生情况,分析老年女性慢性HFpEF患者发生MACE的危险因素。结果 210例患者随访(11.3±2.2)个月,失访22例(10.5%);86例(41.0%)发生MACE,包括5例全因死亡、65例因心力衰竭再入院和16例恶性心律失常。Kaplan-Meier生存分析结果提示,衰弱组患者的MACE发生率和因心力衰竭再入院率均明显高于对照组[51.4%(36/70)比35.7%(50/140)、40.0%(28/70)比26.4%(37/140)](均P<0.05)。多因素Cox回归模型分析结果显示,年龄、血肌酐、白蛋白、B型脑钠肽和衰弱是老年女性慢性HFpEF患者发生MACE的独立危险因素,而β受体阻滞剂是其独立保护因素(均P<...     

沙库巴曲缬沙坦钠对射血分数保留和射血分数降低的心力衰竭合并高血压患者的辅助治疗效果比较

目的 探讨沙库巴曲缬沙坦钠对射血分数保留的心力衰竭（HFpEF）和射血分数降低的心力衰竭（HFrEF）合并高血压患者的辅助治疗效果影响。方法 纳入2019年1月至2021年12月收治的120例心衰合并高血压患者作为研究对象,其中60例HFrEF合并高血压患者作为HFrEF组,60例HFpEF合并高血压患者作为HFpEF组,2组均接受沙库巴曲缬沙坦钠辅助治疗。比较2组患者的临床疗效、治疗前后血压控制水平、心功能指标[左室收缩末期内径（LVESD）、左室舒张末期内径（LVEDD）]、肾功能指标[血清纤维蛋白原（FIB）,肾小球滤过率（GFR）]炎性因子水平[丝氨酸蛋白酶活性域的NLR家族蛋白3信使核糖核酸（NLRP3mRNA）、血清白细胞介素-1β(IL-1β)]、6min步行试验（6MWT）和N末端前体B型钠尿肽（NT-proBNP）,统计不良反应发生率。结果 2组总有效率差异无统计学意义（P> 0.05）。治疗后,HFrEF组的血压明显低于HFpEF组（P <0.05）。2组治疗后的LVESD、LVEDD、FIB较治疗前均显著降低（P <0.05）,GFR显著升高（P...     

沙库巴曲缬沙坦钠与培哚普利治疗慢性射血分数减少心力衰竭的疗效观察

目的研究沙库巴曲缬沙坦钠(ARNI)与培哚普利治疗慢性射血分数减少心力衰竭(HFrEF)患者的疗效。方法 80例HFrEF患者,采用随机数字表法分为观察组和对照组,每组40例。对照组采用培哚普利治疗,观察组采用沙库巴曲缬沙坦钠治疗。观察比较两组患者治疗前后左室射血分数(LVEF)、左室舒张末期内径(LVEDD)、N-末端B型利钠肽(NT-proBNP)水平,治疗效果,不良反应发生情况。结果观察组总有效率为95.0%,明显高于对照组的77.5%,差异有统计学意义(P<0.05)。治疗前,两组LVEDD、LVEF、NT-proBNP水平比较,差异无统计学意义(P>0.05);治疗后,观察组LVEDD(50.10±5.62)mm、NT-proBNP(110.68±75.28)pg/ml均低于对照组的(55.17±6.55)mm、(320.56±68.58)pg/ml, LVEF(50.28±7.20)%高于对照组的(44.62±5.23)%,差异均有统计学意义(P<0.05)。观察组不良反应发生率为30.0%,低于对照组的52.5%,差异有统计学意义(P<0.05)。结论沙库巴曲缬沙坦钠在改善HFrEF患者LVEF、LVEDD及NT-proBNP水平方面效果明显优于培哚普利,且未发现其他明显不良反应。     

低钠血症与慢性心力衰竭的相关性及预后分析

摘要： 目的 分析低钠血症与慢性心力衰竭 （CHF） 的相关性及预后的关系。方法 CHF 住院患者 （CHF 组） 507 例及同期非心衰患者（非心衰组） 212 例, 考察 2 组一般资料情况; 将差异有统计学意义的指标为自变量, 通过多元 Logistic 分析血钠与 CHF 的关系; 随访结果分析血钠与 CHF 患者病死率和再入院率的关系, 并进一步分析血钠与脑 钠肽（BNP）、 左射血分数（LVEF）保留心衰（LVEF≥0.45, HFpEF）和 LVEF 减低心衰（LVEF<0.45, HFrEF）预后的关 系。结果 2 组比较, 性别、 吸烟史等差异无统计学意义（P＞0.05）, 年龄、 血红蛋白、 血钠等差异有统计学意义（P＜ 0.05）; 血钠是 CHF 的保护因素。低钠血症组 （Na+<135 mmol/L） BNP 浓度高于非低血钠组 (P＜0.05); LVEF 差异无统 计学意义。CHF 患者中低钠血症组病死率高于非低血钠组（P＜0.05）, 而再入院率差异无统计学意义（P＞0.05）, HFpEF 患者中低钠血症组和非低血钠组病死率及再入院率差异均有统计学意义 （P＜0.05）。结论 血钠是 CHF 的 保护因素,HFpEF 合并低钠血症者远期更易死亡及再入院。     

射血分数保留型心力衰竭合并心房颤动的研究进展

随着社会经济发展及老龄化程度加重,心力衰竭(心衰)患病率呈上升趋势。过去射血分数降低的心力衰竭(HFrEF)更受人们关注,随着对心衰研究认识深入,射血分数保留的心力衰竭(HFpEF)也越来越受到重视。心衰和心房颤动(房颤)关系错综复杂,两者发生先后至今尚无定论。心衰各亚型中HFpEF与房颤关系更为密切,关于HFpEF合并房颤的研究相对较少。该研究从流行病学、病理生理机制和治疗进展等方面对HFpEF合并房颤进行了综述,以期为HFpEF合并房颤病人的管理及预后提供帮助。     

慢性心衰患者血清GDF-15与PⅠCP、 PⅢNP的相关性分析

目的 检测心力衰竭（心衰）患者血清生长分化因子15（GDF-15）与Ⅰ型前胶原羧基端肽（PⅠCP）、Ⅲ型前 胶原氨基端肽（PⅢNP）的变化并分析其相关性,探究GDF-15对心衰患者心室重构的指导作用。方法 纳入219例 心衰患者,按照美国纽约心脏病协会（NYHA）心功能分级分为NYHAⅠ级组58例、Ⅱ级组39例、Ⅲ级组47例、Ⅳ级组 75例;按左室射血分数（LVEF）分为射血分数减低的心衰组（LVEF＜0.45,HFrEF组,69例）和射血分数保留的心衰组 （LVEF≥0.45,HFpEF组,150例）;选取32例同期健康体检者作为对照组。采用ELISA法检测血清GDF-15、PⅠCP、P ⅢNP 水平,超声心动图测量左室舒张末期内径（LVEDD）、左心房内径（LA）、室间隔厚度（IVST）、左室后壁厚度 （LVPWT）以及 LVEF,计算左室质量指数（LVMI）,并分析心衰患者血清 GDF-15 与 PⅠCP、PⅢNP、NT-proBNP、 LVEDD、LA、LVMI及LVEF的相关性。结果 心衰患者血清NT-proBNP、GDF-15、PⅠCP、PⅢNP水平随NYHA分级 增加而升高（P＜0.05）。对照组、HFpEF组和HFrEF组LA、LVEDD、LVMI、NT-proBNP、GDF-15、PⅠCP及PⅢNP依 次升高（P＜0.05）。心衰患者血清GDF-15水平与PⅠCP、PⅢNP、NT-proBNP、LA、LVEDD、LVMI呈正相关（rs分别为 0.549、0.533、0.539、0.393、0.403、0.485,均 P＜0.01）,与 LVEF 呈负相关（rs=-0.568,P＜0.01）。结论 心衰患者血清 GDF-15与心衰严重程度相关,并可反映心衰患者心室重构情况。     

老年慢性心力衰竭病人血清hs-cTnI、MMP-9、sST2水平检测及临床意义

目的 探究老年慢性心力衰竭病人血清高敏肌钙蛋白T(hs-cTnI)、基质金属蛋白酶-9(MMP-9)、可溶性基质溶素-2(sST2)水平检测及临床意义。方法 选取解放军联勤保障部队第九二〇医院2017年5月至2021年6月收治的100例老年慢性心力衰竭病人作为观察组,心功能分级为Ⅱ～Ⅳ级,其中Ⅱ级32例,Ⅲ级34例,Ⅳ级34例;另选取该院同期体检的心功能正常且无心脏病的老年人60例作为对照组。比较两组临床资料、血清hs-cTnI、MMP-9、sST2水平,分析老年慢性心力衰竭影响因素,评价血清hs-cTnI、MMP-9、sST2水平对老年慢性心力衰竭的诊断价值,并比较不同心功能分级病人血清hs-cTnI、MMP-9、sST2水平。结果 两组性别、年龄、体质量指数（BMI）、血胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、吸烟史、高血压及糖尿病比例比较,差异无统计学意义（P>0.05）;观察组血清脑钠肽（BNP）(535.63±60.87)ng/L水平高于对照组（78.62±25.41）ng/L,左室射血分数（LVEF）(49.83±5.47)...     

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.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

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.