Effects of Maillard reaction and its product AGEs on aging and age-related diseases

Maillard reaction(MR)is a non-enzymatic browning reaction commonly seen in food processing,which occurs between reducing sugars and compounds with amino groups.Despite certain advantages based on Maillard reaction products(MRPs)found in some food for health and storage application have appeared,however,the MR occurring in human physiological environment can produce advanced glycation end products(AGEs)by non-enzymatic modification of macromolecules such as proteins,lipids and nucleic acid,which could change the structure and functional activity of the molecules themselves.In this review,we take AGEs as our main object,on the one hand,discuss physiologic aging,that is,age-dependent covalent cross-linking and modification of proteins such as collagen that occur in eyes and skin containing connective tissue.On the other hand,pathological aging associated with autoimmune and inflammatory diseases,neurodegenerative diseases,diabetes and diabetic nephropathy,cardiovascular diseases and bone degenerative diseases have been mainly proposed.Based on the series of adverse effects of accelerated aging and disease pathologies caused by MRPs,the possible harm caused by some MR can be slowed down or inhibited by artificial drug intervention,dietary pattern and lifestyle control.It also stimulates people's curiosity to continue to explore the potential link between the MR and human aging and health,which should be paid more attention to for the development of life sciences.

Hypothalamic circuits and aging:keeping the circadian clock updated

Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from cellular stress and circadian derangements.The circadian clock emerges as a key regulator,sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes,such as stem-cell function,cellular stress responses,and inter-tissue communication,which become disrupted during aging.Given the crucial role of hypothalamic circuits in regulating organismal physiology,metabolic control,sleep homeostasis,and circadian rhythms,and their dependence on these processes,strategies aimed at enhancing hypothalamic and circadian function,including pharmacological and non-pharmacological approaches,offer systemic benefits for healthy aging.Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions,like the hypothalamus,while reducing side effects associated with systemic drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.

Aging effects on QT interval： Implications for cardiac safety of antipsychotic drugs

ObjectivesTo 明确地在心脏的毒性上探索老化的效果年龄和抑制精神的药的相互作用与搜索策略用 OvidSP 平台被寻找改变 QT interval.MethodsThe Medline 数据库：“； QT interval”；或 “； QT”；并且 “； age”；或 “； aging”；。入口标准是：有两性上的数据的超过 10,000 个显然健康的个人；为心率(QTc ) 和它的变化的表情改正延续到更旧的 ages.ResultsQTc 的多重年龄十年的 QT 间隔与增加年龄在持续时间增加了。在正常人口在 QTc 认为谦虚的是 SD 增长，氯普马嗪的增加生产了比好久 70 岁以上的 450 ms 平均大的 QTc。Risperidone，那平均没改变 QTc，将被期望在一些情形下面在他们的 70 年中年里在人生产 450 ms 的 QTc。QTc 延伸 >；有抑制精神的药的 500 ms 在 99 th 百分位数。当与抑制精神的药导致的期望的 QT 间隔变化的范围结合了时，它可以与平均不在显然正常的老人或女人为 QT 间隔改变价值的 QTc.ConclusionsThe 范围的 Haloperidol 发生，能乐意地与延长 QTc 被联系。有在 99 th 百分位数可以与甚至不是的那些通常与 QTc 延伸联系了的抑制精神的药有严肃的 QTc 延伸。

Clinical Study on the Needling and Drug Treatment of Acute Cerebral Hemorrhage

Researches in recent years have shown that cellular immune factor plays an important role in the generation and development of cerebral hemorrhage1-3.

A review of age-old antimalarial drug to combat malaria:efficacy upgradation by nanotechnology based drug delivery

Malaria is uncontrolled burden in the world till now.Despite of different efforts to develop antimalarial drug for decades,any anti-malarial drug can able to eradicate completely till now.Many anti-malarial substances are practically ineffectual because of their physicochemical limitations,cytotoxicity,chemical instability and degradation,and limited activities against intracellular parasites.Taking into consideration,the amount of research is going to conduct in the field of nanoparticle based drug delivery systems,lead to new ways of improving the treatment of infectious diseases.The study has focused on the progress and advancement of research on nanotechnology based drug delivery to eradicate the malaria.We like to focus the efficacy of nanotechnology based drug application for the opening out of novel chemotherapeutics in laboratory research,which may show the way to better use with age-old antimalarial drug and may draw the attention of pharmaceutical industries for the improvement and designing of effective anti-malarial drugs in future.

Drug Utilization in Homes for the Aged in Brasilia, Brazil

This paper aims to describe the socioeconomic and epidemiological profile, as well as the standards of medicine consumption in a group of 154 elderly people from five homes for the aged in Brasilia, in order to expand the understanding about some characteristics and individual needs of this population and its influence on the quality of drug’s therapy. Data were collected between January and December of 2007, it was used a questionnaire adapted from Dader’s method (2002) and a pharmacotherapeutic follow up method and it was responded by the elders and caregivers. Data were supplemented with information from medical records and prescriptions available in the institutions. The studied group has an average age of 74.6 years, living in their current homes for about 5.4 years and the group consists mainly of men with preserved cognitive status. The members of the group have low monthly income, low education level and are sedentary. They consume 4 - 5 drugs and are affected mainly by cardiovascular and psychiatric diseases. Results suggest that low monthly income, low education level, the prevalence of sedentary lifestyle, elders with compromised cognitive status, the increasing number of chronic diseases and the high consumption of drugs in the researched group may be important factors for the emergence or injury drugs-related problems (DRP) as non-adherence to treatment, medication errors, drug interactions and adverse drug reactions compromising the quality of medication therapy. This study points out the necessity of including a pharmacotherapeutic follow-up for the elderly people in order to minimize such problems and provide better quality of life for patients.

关注新生血管性年龄相关性黄斑变性的创新药物治疗

湿性年龄相关性黄斑变性(nAMD)是老年人致盲的主要原因,抗VEGF是其主要治疗方法。目前,nAMD治疗仍面临诸多不足和挑战,开发新的治疗药物和给药方法是其主要研究的方向。近年来治疗nAMD的药物研发方向呈现多样化,包括开发新靶点/新机制药物及新型给药方式、优化给药剂量和基因疗法等,达到降低治疗频率、延长治疗间隔、提高患者治疗依从性和长期维持或改善视力的目的。眼科临床医师应对新的药物有较为全面的了解,进而发掘出适合不同nAMD亚型患者的优化方案,实现向精准化医疗迈进。

临床医生应重视老年人心脏淀粉样变的诊断与处理

心脏淀粉样变(CA)是淀粉样蛋白错误折叠沉积于心肌细胞外基质所致的心脏疾病。CA好发于老年人,由于症状缺乏特异性且既往被认为是一种罕见病,老年CA患者极易被误诊和漏诊。近年来随着对该病诊断意识的提高及无创性影像学诊断方法的进步,诊断为CA的患者有所增加;治疗CA的药物研究也有重大突破,研发了多种特异性治疗药物。早期治疗可以防止淀粉样蛋白进一步沉积导致的器官损伤,从而改善老年CA患者预后。因此,临床医生应该充分了解老年CA患者的临床特征,重视老年CA的诊断及治疗。

《中国老年代谢综合征药物治疗专家共识(2022)》解读

老年代谢综合征是一组复杂的代谢紊乱症候群,其作为一种共病发病率高,临床表现多样,机制复杂且涉及联合用药,发生药物不良反应的风险高。老年代谢综合征严重损害老年人的生活质量和健康,给我国医疗系统及社会造成沉重的负担。《中国老年代谢综合征药物治疗专家共识(2022)》全面梳理和总结了老年代谢综合征的诊断标准和治疗目标、最新治疗药物及其相互作用,并做出10条推荐意见。该文就共识要点特别是药物治疗方面进行解读,以期为老年代谢综合征药物治疗决策与健康管理提供相关参考。

沙盘游戏联合药物干预对学龄期ADHD患儿负性情绪及行为管理能力的影响

目的研究沙盘游戏疗法联合药物干预对学龄期注意缺陷多动障碍(ADHD)患儿负性情绪及行为管理能力的影响。方法选取2019年6月至2022年1月于本院治疗的120例ADHD患儿为研究对象,将其随机分为观察组和对照组,每组60例。对照组给予药物治疗,观察组在对照组的基础上进行沙盘游戏干预。分别于干预前后比较2组患儿症状积分[中文版注意缺陷多动障碍筛查量表(SNAP-IV)父母版]、情绪状态[儿童焦虑性情绪障碍筛查表(SCARED)和儿童抑郁障碍自评量表(DSRSC)]和行为管理能力。结果干预后,观察组对抗性行为、多动-冲动、注意力不集中症状积分和SCARED得分、DSRSC得分均明显低于对照组(P<0.05),注意力商数、控制力商数、综合控制力商数和综合注意力商数明显高于对照组(P<0.05)。结论沙盘游戏疗法联合药物干预可有效改善学龄期ADHD患儿各项临床症状,缓解患儿焦虑、抑郁等不良情绪,提高患儿行为管理能力。

Pathogenic and therapeutic role of exosomes in neurodegenerative disorders

Neurodegenerative disorders affect millions of people worldwide,and the prevalence of these disorders is only projected to rise as the number of people over 65 will drastically increase in the coming years.While therapies exist to aid in symptomatic relief,effective treatments that can stop or reve rse the progress of each neurodegenerative disease are lacking.Recently,research on the role of extracellular vesicles as disease markers and therapeutics has been intensively studied.Exosomes,30-150 nm in diameter,are one type of extracellular vesicles facilitating cell-to-cell communication.Exosomes are thought to play a role in disease propagation in a variety of neurodegenerative diseases,such as Alzheimer's disease,Parkinson s disease,and amyotrophic lateral sclerosis.Accordingly,the exosomes derived from the patients are an invaluable source of disease biomarkers.On the other hand,exosomes,especially those derived from stem cells,could serve as a therapeutic for these disorders,as seen by a rapid increase in clinical trials investigating the therapeutic efficacy of exosomes in different neurological diseases.This review summarizes the pathological burden and therapeutic approach of exosomes in neurodegenerative disorders.We also highlight how heat shock increases the yield of exosomes while still maintaining their therapeutic efficacy.Finally,this review concludes with outstanding questions that remain to be addressed in exosomal research.

老年髋部骨折患者术后抗骨质疏松药物治疗现状及关联因素分析:一项全国多中心现况调查研究

背景抗骨质疏松药物治疗是预防老年髋部骨折患者再骨折发生的重要手段,术后抗骨质疏松药物治疗的现状和关联因素尚不清楚。目的明确我国老年髋部骨折患者术后抗骨质疏松药物治疗的现状和关联因素。方法通过多阶段整群抽样法,调查全国31个省(自治区/直辖市)的594所医院骨质疏松性骨折患者,从中选取60岁以上髋部骨折手术患者作为调查对象。调查内容包括患者基本信息和骨折管理信息。采用多因素Logistic回归分析抗骨质疏松药物治疗的关联因素。结果共计4369例老年髋部骨折患者纳入研究,其中女性3000例,男性1369例。患者平均年龄(76.48±8.78)岁。患者的抗骨质疏松药物治疗率为21.8%。抗骨质疏松药物治疗的关联因素包括地区(华南vs华东,OR=0.64,95%CI:0.45~0.91;华中vs华东,OR=0.50,95%CI:0.37~0.68)、医院类别(综合医院vs专科医院,OR=1.77,95%CI:1.22~2.57)、家庭年收入[(10~20)万元vs<10万元,OR=1.48,95%CI:1.21~1.82;(20~30)万元vs<10万元,OR=2.11,95%CI:1.51~2.94;>30万元vs<10万元,OR=2.14,95%CI:1.48~3.09]、合并肺炎(OR=1.99,95%CI:1.43~2.78)、合并脑卒中(OR=0.65,95%CI:0.45~0.93)、合并眼部疾病(OR=1.84,95%CI:1.10~3.06)、骨折风险评估史(OR=1.40,95%CI:1.02~1.93)、骨质疏松症知识知晓水平高(OR=1.26,95%CI:1.06~1.50)、骨折后使用钙片/维生素D(OR=5.32,95%CI:4.18~6.76)和院内骨密度检测(OR=2.94,95%CI:2.46~3.51)。结论我国老年髋部骨折患者术后抗骨质疏松药物治疗率较低。地区、医院类别、家庭年收入、合并症、骨折风险评估史、骨质疏松症知识知晓水平、骨折后使用钙片/维生素D和院内骨密度检测和是老年髋部骨折患者抗骨质疏松药物治疗的关联因素。

地西他滨联合小剂量HAG方案治疗老年急性髓系白血病疗效研究

目的:观察国产地西他滨联合小剂量HAG方案治疗老年急性髓系白血病的疗效及不良反应。方法:回顾性分析我中心2014年4月至2016年12月收治的80例老年急性髓系白血病患者的临床资料,依据用药方法不同分成观察组和对照组,观察组采用国产地西他滨联合小剂量HAG方案治疗,对照组采用传统MA方案治疗。观察两组患者的疗效及不良反应发生情况。结果:观察组患者接受国产地西他滨联合小剂量HAG方案治疗后的完全缓解率及部分缓解率均显著高于对照组(P<0.05);化疗后粒细胞缺乏时间以及肺部感染发生率明显低于对照组(P<0.05);两组化疗方案所致肝肾毒性、消化道反应等非血液学不良反应均可耐受,无统计学差异(P>0.05)。结论:国产地西他滨联合小剂量HAG方案治疗老年急性髓系白血病有效率较高,不良反应较轻,安全性高,临床值得推广。

ATF5蛋白表达水平与胃癌AGS细胞药敏水平的相关性

目的:探究ATF5蛋白表达水平与胃癌AGS细胞药敏水平的相关性。方法:采用脂质体载体转染技术转染ATF5 pc DNA3.1质粒、ATF5 si RNA空质粒,构建ATF5蛋白高、中、低表达水平的AGS细胞组。Western blot实验检测AGS细胞中ATF5蛋白表达水平,MTT实验检测AGS细胞对紫杉醇、顺铂药物敏感性,平板克隆形成实验探讨AGS细胞集落形成差异,分析ATF5蛋白表达水平与胃癌AGS细胞药敏水平的相关性。结果:ATF5蛋白过表达组AGS细胞在紫杉醇、顺铂影响后存活率较对照组高,均P<0.05,IC50值较对照组也明显升高,均P=0.00;而低表达组存活率较对照组低,均P<0.05,IC50值较对照组也明显降低,P顺=0.00,P紫=0.002。过表达组细胞在药物影响后克隆形成数较对照组高,而低表达组克隆形成集落较对照组低,均P<0.05。结论:ATF5蛋白的过表达能降低胃癌AGS细胞对紫杉醇、顺铂的药物敏感性,而ATF5蛋白的低表达则能增加胃癌AGS细胞对紫杉醇、顺铂的药物敏感性,提示胃癌AGS细胞药敏水平可能与ATF5蛋白表达水平相关。

药物涂层球囊治疗老年患者冠状动脉大血管原位病变的有效性和安全性:一项队列研究

背景近年来,随着人口老龄化程度加深,老年患者冠状动脉大血管病变的发病率显著增加。药物涂层球囊(DCB)作为一种新兴治疗手段,因其能有效减少再狭窄发生率而备受关注。然而,现有研究多集中于小血管病变,对大血管原位病变的有效性数据较少。目的探讨DCB治疗老年患者冠状动脉大血管原位病变的效果。方法回顾性选取2022年就诊于内蒙古医科大学附属医院行经皮冠状动脉介入治疗(PCI)且年龄>60岁老年冠心病(CHD)患者128例为研究对象。完善术前检查化验。按照PCI治疗方案分为DCB组(n=30)、药物洗脱支架(DES)组(n=64)和生物可吸收支架(BVS)组(n=34)。术前、术后即刻及术后随访分别进行冠状动脉造影(CAG),观察术前靶血管参考直径(RVD),术前、术后即刻及术后1年随访观察最小管腔直径(MLD),进一步推算术前直径狭窄程度(DS)、术后即刻观察管腔获益(AG),术后即刻与术后随访1年残余直径狭窄程度(RDS)和晚期管腔丢失(LLL)。随访期间每月定期门诊或电话随访,记录患者院内及出院后1年内患者主要不良心血管事件(MACE)。采用LASSO回归分析筛选相关变量后,采用多因素Logistic回归分析探究MACE发生的影响因素。采用Kaplan-Meier法绘制患者发生MACE的生存曲线,生存曲线的比较采用Log-rank检验。结果DCB组、DES组和BVS组患者基线资料比较,差异无统计学意义(P>0.05)。术后即刻BVS组MLD、AG高于DCB组、DES组,RDS低于DCB组、DES组(P<0.05),术后1年DES组RDS低于DCB组(P<0.05)。3组患者院内均无MACE发生,术后中位随访时间为478(425,538)d,共发生38例MACE,随访期间3组均无心肌梗死与心源性死亡事件发生;出血事件:DCB组有0例,DES组有3例,BVS组有3例,表现为牙龈出血,经评估为轻度出血。Log-rank检验结果示3组患者无MACE存活率比较,差异无统计学意义(P=0.580)。LASSO回归分析筛选低密度脂蛋白胆固醇(LDL-C)、介入治疗史纳入多因素Logistic回归分析,结果示LDL-C(OR=12.204,95%CI=3.403~43.768)、介入治疗史(OR=0.041,95%CI=0.010~0.162)是患者发生MACE的影响因素。结论DCB治疗老年CHD患者大血管病变与DES和BVS比较无明显差异,有效性及安全性DES和BVS相当。DCB是治疗老年患者冠状动脉大血管病变安全、有效的方式,LDL-C升高和介入治疗史是MACE发生的影响因素。

脑卒中后癫痫患者发生抗癫痫药物耐药的预测因素分析

目的:分析脑卒中后癫痫(PSE)患者发生抗癫痫药物耐药的预测因素。方法:收集2017年1月至2021年1月郑州大学第五附属医院收治的141例PSE患者。根据国际抗癫痫联盟对于抗癫痫药物耐药的判定标准将患者分为耐药组(n=23)与非耐药组(n=118)。采用Logistic回归分析PSE患者发生抗癫痫药物耐药的影响因素,并分析筛选出的影响因素对PSE患者发生抗癫痫药物耐药的预测价值。结果:Logistic回归分析显示,脑卒中首发年龄≤50岁、出血性脑卒中、中重度脑卒中是PSE患者发生抗癫痫药物耐药的危险因素[OR(95%CI)分别为1.226(1.108~1.356)、6.866(1.197~39.390)、0.073(0.013~0.417)]。脑卒中首发年龄≤50岁、出血性脑卒中对PSE患者发生抗癫痫药物耐药的预测价值较高,敏感度和特异度分别为0.826和0.848,0.739和0.780。结论:脑卒中首发年龄≤50岁、出血性脑卒中对于PSE患者发生抗癫痫药物耐药具有良好的预测价值。

AGEs平台筛选中药及中药有效成分

目的 寻找抑制AGEs形成的中药及中药有效成分。方法 通过分析现有国内报道抑制AGEs形成的化合物的结构特点和作用机制 ,利用体外AGEs形成的模型 ,进行中药及中药有效成分的筛选。结果 川芎素、复方丹参注射液等中药及中药有效成分对体外AGEs形成有很好的抑制作用 ,大蒜素、维生素C等对体外AGEs的形成未见抑制作用 ,而维生素B1、维生素B6、维生素B12 对体外AGEs的形成有一定的促进作用。结论 具有能和AGEs的前体羰基化合物反应的中药及中药有效成分可以抑制体外AGEs的形成。

基于Beers标准(2019版)评价河北省多种慢性病共存老年心力衰竭住院患者的潜在不适当用药

目的基于Beers标准(2019版)对河北地区多种慢性病共存老年心力衰竭(简称心衰)住院患者的潜在不适当用药(PIM)进行调查,并结合各疾病专科诊疗指南进行深入分析,探讨其相关危险因素,为促进多种慢性病共存老年人群临床合理用药提供参考。方法2022年1月随机从河北省4家医疗机构信息系统中各抽取50例老年心衰住院患者的电子病历资料。根据纳入与排除标准,最终纳入135例符合标准的患者。基于Beers标准(2019版)对老年心衰住院患者的PIM情况进行评估,结合疾病诊疗指南深入用药分析评价,给出用药建议。采用多因素Logistic回归分析老年心衰住院患者发生PIM的影响因素。结果不同年龄、罹患疾病种类的老年心衰住院患者PIM发生率比较,差异均无统计学意义(P>0.05);不同性别、用药种类、肾小球滤过率(GFR)的老年心衰住院患者PIM发生率比较,差异均有统计学意义(P<0.05)。按PIM发生频率高低排序前3位依次为利尿剂、螺内酯、苯二氮[艹卓]类镇静催眠药物。38例患者存在53例次PIM,排名前3的药物分别为苯二氮[艹卓]类镇静催眠药物、地高辛和抗精神病药物。24例患者存在26例次PIM,其中慢性肾脏病4期或以上阶段患者使用非甾体抗炎药物、心衰患者使用非甾体抗炎药物、晕厥患者使用胆碱酯酶抑制剂的情况较多。86例患者存在117例次高风险用药,其中老年住院患者使用利尿剂情况最多;其次为≥75岁的患者使用新型口服抗凝药物利伐沙班及达比加群。21例患者存在22例次药物相互作用,其中老年住院患者联合使用肾素-血管紧张素系统抑制剂和保钾利尿剂情况最多,共出现12例次。22例肾功能不全患者存在25例次PIM情况,其中肌酐清除率<30 mL/min的老年住院患者使用螺内酯的情况最多,共出现14例次。多因素Logistic回归分析结果显示,回归方程的拟合度为83.2%,其中女性、用药种类≥20种、GFR<45 mL/(min·1.73 m^(2))是发生PIM的危险因素(P<0.05)。结论河北地区多种慢性病共存老年心衰住院患者的PIM发生率较高,女性、用药种类≥20种、GFR<45 mL/(min·1.73 m^(2))是发生PIM的危险因素,合理用药水平有待提高。

基于Web of Science的药品说明书适老化研究文献计量学分析

目的探索药品说明书适老化的研究热点,为我国药品说明书适老化发展提供依据。方法在Web of Science核心合集数据库中检索2012-2022年发表的老年人使用药品说明书的相关英文文献,应用VOSviewer和CiteSpace软件进行文献计量学分析,探索该领域的研究热点,并总结该领域发展的障碍和解决措施。结果与结论本研究共收集到药品说明书适老化相关文献335篇,来自51个国家(地区)的819个研究机构,涉及2174位作者。近10年,药品说明书适老化研究发展趋缓,美国和日本等发达国家占该领域的主导地位,其中美国西北大学Wolf等学者的发文量最大(12篇)。老年人用药风险管理、药品说明书中老年用药信息的更新,以及老年人对药品说明书的理解和依从及其影响因素等是该领域的研究热点。药品说明书适老化发展中相关障碍的解决措施包括提高药品说明书的可视性、可读性,填补药品说明书中老年用药信息等。我国可借鉴其他国家的经验和方法,针对我国人口特点开展老年药品说明书影响因素的调查及老年用药的药动学研究,多维度提高老年患者用药的安全性。