内蒙古地区蒙汉族儿童正常人群HLA-DRB1基因多态性研究

目的 研究内蒙古地区蒙、汉族儿童正常人群HLA-DRB1等位基因的分布概况。方法 采用分析性研究策略，引入PCR-SSP技术，对祖籍三代居住内蒙古地区，无血缘关系和与异族通婚史的蒙、汉族正常健康儿童102名和108名进行HLA-DRB1等位基因的型别分析和比较。结果 (1)蒙、汉族HLA-DRBl各等位基因均被检出；(2)蒙古族HLA-DRB1基因频率较高的依次是*040x(14．9％)、*120x(13．7％)和*150x(10．3％)，而较低的等位基因依次是：*1001(2％)、*160x(2％)和*010x(3．5％)；汉族HLA．DRBl基因频率较高的等位基因依次是：*090l(15％)、*150x(13．4％)和*040x(11．8％)，而较低的等位基因依次是：*1001(3．8％)、*070x(4．2％)和*160x(4．2％)；(3)蒙古族HLA-DRB1*070x和*120x基因频率分别为9．2％和13．7％，高于汉族相应的4．2％和5．7％(χ^2分别是4．061和7．318，P分别是0．044和0．007)，差异有统计学意义。而汉族DRB1*0901基因频率为15％，高于蒙古族4．5％(χ^2=12．462，P=0．000)，差异有非常显著意义；(4)蒙、汉族间遗传距离(D)为0．253。结论 内蒙古地区蒙、汉族儿童健康人群中HLA-DRB1等位基因分布不同，但差异不大，符合中华民族是一个统一整体这一事实。     

支气管哮喘HLA-DRB1等位基因研究

目的:研究山西汉族支气管哮喘患者的HLA-DRB1等位基因的频率.方法:采用顺序特异引物聚合酶链反应(PCR/SSP)技术检测山西汉族64例支气管哮喘患者HLA-DRB1等位基因频率,并与山西正常人群进行比较分析.结果:支气管哮喘组HLA-DRB1*1501/1502基因频率明显增高(P<0.05),为23.44%;其它等位基因频率在两组间无显著差异.结论:在山西汉族人群中HLA-DRB1*1501/1502与支气管哮喘相关联.     

HLA-DRB1、HLA-DQB1基因多态性与云南汉族人群耐多药肺结核病的关联研究

摘要：目的:探讨云南地区汉族人群HLA-DRB1、HLA-DQB1基因多态性与耐多药肺结核病发生的关系。方法:收集2017～2018年在我院就诊的云南省汉族耐多药肺结核（MDR-PTB）患者300例作为观察组;门诊体检健康人群300例作为对照组。应用聚合酶链式反应-直接测序基因分型法（PCR-SBT）,检测两组人群HLA-DRB1、HLA-DQB1等位基因分布频率。结果:共检测到25个HLA-DRB1等位基因,17个HLA-DQB1等位基因。其中观察组的HLA-DRB1*07:01等位基因频率显著性高于对照组[18.7%vs.13.5%,P=0.007,OR=1.471,95%CI（1.077,2.008）],观察组的HLA-DQB1*03:01等位基因频率显著性高于对照组[27.8%vs.20.3%,P=0.002,OR=1.511,95%CI（1.157,1.974）],其余等位基因两组间无明显差异（P>0.05）。结论:HLA-DRB1*07:01和HLA-DQB1*03:01等位基因可能是云南汉族人群耐多药肺结核的易感基因。     

HLA-DRBl等位基因多态性对乙型肝炎患者预后的影响

目的研究HLA-DRBl等位基因多态性与河南汉族乙型肝炎预后的相关性。方法以河南汉族慢性乙型肝炎、乙型肝炎病毒携带者、原发性肝癌、健康组对照组为研究对象,应用聚合酶链反应-序列特异性引物技术（PCR-SSP）对研究对象的HLA-DRB1等位基因多态性进行分析比较。结果 HLA-DRB1＊0701、1001、1201、1501在河南汉族慢性乙型肝炎组分布频率显著高于健康对照组（P〈0.05）,而HLA-DRB1＊1301（2）显著低于健康对照组（P〈0.05）;HLA-DRB1＊0701、1001、1201、1501在河南汉族慢性乙型肝炎和乙型肝炎病毒携带者组分布频率差异无统计学意义（P〉0.05）;HLA-DRB1＊1501在原发性肝癌组分布频率显著高于健康对照组（P〈0.05）,RR=13.72。结论等位基因HLA-DRB1＊0701、1001、1201、1501是河南汉族慢性乙型肝炎和乙型肝炎病毒携带者的易感基因,HLA-DRB1＊1501是原发性肝癌的易感基因,HLA-DRB1＊1301（2）是河南汉族乙型肝炎的保护性基因     

小儿热性惊厥对HLA-Ⅱ类基因的遗传易感性

目的探索小儿热性惊厥（FC）的HLA-DOA1和HLA-DRB1等位基因的遗传易感性，揭示其遗传背景。方法采用病例对照研究策略．引入PCR-SSP技术．在祖籍三代居住包头地区，无血缘关系，无与异族通婚史及其他神经和免疫系统疾病史和家族史的汉族人群中，选择53例FC为病例组，53名健康儿童为对照组，作以HLA-DOA1和HLA-DRB1等位基因的型别分析。基因频率比较在单因素分析的基础上又作以多因素Lo-Nsac回归。结果病例组HLA-DQA1＊0101基因频率为8．5％，比对照组的1．9％高，P=0．047〈0．05。B=1．566〉0．OR=4．789〉1，其95％可信区间为1．021～22．547，其内不包含1。EF=0．647〉0。促进发病；而HLA-DQA1＊0401基因频率在病例组为0．9％，比对照组的8．5％低，P=0．035〈0．05。B=-2．240〈0，OR=0．106〈1，其95％可信区间为0．013～0．857，其内不包含1。PF=0．458〉0。阻止发病。HLA-DRB1基因频率比较均P〉0．05，OR的95％可信区间内亦包含1。结论HLA-DQA1＊0101等位基因可能是包头地区小儿FC发病单体型中一个遗传易感基因；而HLA-DOA1＊0401等位基因可能为其保护基因。HLA-DRB1等位基因与FC发病无关联性。     

人类白细胞抗原-DRB1基因多态性与家族性乙型肝炎相关性研究

目的探讨人类白细胞抗原(HLA)-DRB1基因多态性与家族性乙型肝炎的相关性。方法采用聚合酶链反应-特异性序列寡核苷酸(PCR-SSO)探针基因分型方法结合荧光磁珠流式检测技术,对山西地区汉族家族性乙型肝炎家庭的143例患者,进行HLA-DRB1等位基因13个位点检测,用统计学方法对检测结果进行分析。结果慢性乙型肝炎组HLA-DRB1*07等位基因频率(17.8%)明显高于正常对照组(7.4%),两者相比差异有统计学意义(P<0.05,OR=2.725);慢性乙型肝炎组HLA-DRB1*04及HLA-DRB1*13等位基因频率(5.1%;0.0%)明显低于正常对照组(16.2%;4.4%),差异有统计学意义(P<0.05,OR=0.278;P<0.05);其他型别的等位基因在各组间差异无统计学意义。结论HLA-DRB1*07与家族性乙型肝炎易感性密切相关,可能是家族性乙型肝炎的易感基因或连锁基因;HLA-DRB1*04、HLA-DRB1*13与家族性乙型肝炎抗性相关,可能是家族性乙型肝炎的抗性基因。宿主的HLA-DRB1基因可能是预测家族性乙型肝炎预后的主要指标。     

变应性鼻炎患者HIA-DRB1等位基因多态性分析

为探讨遗传因素在变应性鼻炎(AR)发病中的作用，采用PCR／SSP技术对35例东北汉旗人AR患进行了HLA-DRB 1等位基因多态性分析．并与94例健康人作对比。结果发现，AR组HLA-DRBi*0101-2基因频率为12．86％，表型频率为25．21%，RR=17．25(校正P值<4×10^-4);HLA-DRB1*0302基因频率为11．43%，表型频率为5．71%，RR=12．00(校正P值<0．05)；其它等位基因频率在AR组与对照组间差异无显性。结论：HLA-DRB1*0101-2和*0302等位基因与AR相关。     

HLA-DRB1等位基因多态性对乙型肝炎患者预后的影响

目的 研究HLA-DRB1等位基因多态性与河南汉族乙型肝炎预后的相关性。方法 以河南汉族慢性乙型肝炎、乙型肝炎病毒携带者、原发性肝癌、健康组对照组为研究对象,应用聚合酶链反应-序列特异性引物技术(PCR-SSP)对研究对象的HLA-DRB1等位基因多态性进行分析比较。结果 HLA-DRB1*0701、1001、1201...     

HLA-DQA1基因与小儿支气管哮喘及其严重程度的相关性研究

目的探索内蒙古地区汉族小儿支气管哮喘（BA）及其间歇发作和重度发作与HLA-DQA1等位基因的相关性,以寻找相关基因,探寻其部分发病机制及防治前景。方法采用病例对照研究策略,引入聚合酶链反应-序列特异引物法技术,选择小儿BA 66例为病例组（间歇发作42例,重度发作24例）和96名健康小儿,作HLA-DQA1等位基因的型别比较分析。基因频率比较在单因素四格表χ2或Fisher检验的基础上作多因素Logistic回归分析。结果病例组小儿BA、间歇发作和重度发作的HLA-DQA1＊0401基因频率分别为9．1%、9．5%和8．3%．与对照组的1%比较,χ2分别为12．260、9．849、—,P值分别为0．000、0．002和0．016。回归后,Wald分别为6．836、5．469和6．237,P值分别为0．009、0．019和0．013,均P＜0．05。B分别为2．048、1．923和2．205．均B＞0,OR分别为7．754、6．844和9．072,均OR＞1,其95%可信区间分别为1．670～36．005、1．365～34．310和1．607～51．212,其内均不包含1。EF分别为0．746、0．683和0．593,均EF＞0;而病例组小儿BA及其间歇发作的HLA-DQA1＊0103基因频率分别为7．6%和4．8%,与对照组的17．7%比较,χ2分别为6．843和8．250．P值分别为0．009和0．004。回归后．Wald分别为5．841和6．898,P值分别为0．016和0．009,均P＜0．05。B分别为-0．967和-1．469．均B＜0,OR分别为0．380和0．230,均OR＜1,其95%可信区间分别为0．174～0．833和0．077～0．689,均内均不包含1。PF分别为0．271和0．260,均PF＞0。结论HLA-DQA1＊0401等位基因可能是内蒙古地区汉族小儿BA及其间歇发作和重度发作发病单体型中的一个遗传易感基因,而HLA-DQA1＊0103可能为小儿BA及其间歇发作的保护基因。     

HLA-DRB1等位基因分型与类风湿关节炎相关性研究

目的探讨HLA-DRB1等位基因在皖籍江淮地区类风湿关节炎患者的分布及意义。方法采用SSP（序列特异性引物）多重PCR技术扩增106例RA患者和340例正常对照HLA-DRB1等位基因,先对HLA-DRB1位点进行低分辨率分型,再进一步对低分亚型HLA-DRB1＊04,DRB1＊10,DRB1＊01和DRB1＊14做高分辨率分型。计算并比较两组等位基因携带率。结果低分结果共13个亚型,其中HLA-DRB1＊04,DRB1＊09和DRB1＊10在RA组的频率显著高于正常对照组（P=0.005,0.039,0.000）HLA-DRB1＊11,DRB1＊15和DRB1＊07的频率显著低于对照组（P=0.005,0.036,0.001）。HLA-DRB1＊01,DRB1＊14在两组差别无显著意义（P=0.432和P=0.359）。高分结果HLA-DRB1＊0405和DRB1＊1001在RA组的频率显著高于正常对照组（P=0.001和P=0.000）。结论 HLA-DRB1位点在皖籍江淮地区类风湿关节炎患者中的分布具有丰富的多态性,共同表位等位基因（SE等位基因）HLA-DRB1＊0405、DRB1＊1001及非SE等位基因HLA-DRB1＊09可能是皖籍江淮地区类风湿关节炎患者的易感基因,HLA-DRB1＊11,DRB1＊15和DRB1＊07可能是保护性等位基因。     

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.     

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.     

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.     

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.