Th9与支气管哮喘

支气管哮喘（简称哮喘）是一种由多种细胞如淋巴细胞、嗜酸粒细胞、肥大细胞等及其细胞组分参与的气道慢性炎症疾患,Th2细胞被认为是哮喘发病机制中的主要效应细胞。长期以来,白介素9（IL-9）都被认为是Th2类细胞因子,在变应性疾病,尤其是过敏性哮喘、变应性鼻炎等发病机制中起着重要的作用。近年来研究发现,机体内可能存在着一群新型的不同于目前已知Th1、Th2及Th17等效应细胞,被称之为＂Th9＂细胞。Th9细胞在转化生长因子-β及IL-4联合刺激下分化而来,具有分泌IL-9和IL-10的能力。Th9细胞作为效应性T细胞,在促进组织炎症发生的过程中起着重要作用。现就Th9细胞的生物学功能及与哮喘的关系进行简要综述。     

辅助性T细胞9/白细胞介素-9调控类风湿关节炎中辅助性T细胞17/调节性T细胞免疫平衡的研究进展

RA是以滑膜炎为病理基础的自身免疫病,辅助性T细胞(Th)17和调节性T细胞免疫失衡在其发病机制中发挥重要作用.随着对IL-2从促炎因子到调节免疫耐受因子的重新认识,与IL-2共享γ链的IL-2家族成员IL-9作为一种多效性因子受到越来越多的关注,同时发现其主要来源于一种新型T细胞亚型Th9细胞.许多研究认为Th9/IL-9可能通过调控Th17/调节性T细胞免疫平衡从而参与RA滑膜炎症和病情活动,与RA发生发展有关.本文对Th9/IL-9调控RA患者Th17/调节性T细胞免疫平衡的最新研究进展予以综述.     

Th9与支气管哮喘

支气管哮喘（简称哮喘）是一种由多种细胞如淋巴细胞、嗜酸粒细胞、肥大细胞等及其细胞组分参与的气道慢性炎症疾患,Th2细胞被认为是哮喘发病机制中的主要效应细胞。长期以来,白介素9（IL-9）都被认为是Th2类细胞凶子,在变应性疾病,尤其是过敏性哮喘、变应性鼻炎等发病机制中起着重要的作用。近年来研究发现,机体内可能存在着一群新型的不同于目前已知Thl、Th2及Thl7等效应细胞,被称之为“Th9”细胞。Th9细胞在转化生长因子β及L-4联合刺激下分化而来,具有分泌IL-9和IL-10的能力。Th9细胞作为效应性T细胞,在促进组织炎症发生的过程中起着重要作用。现就Th9细胞的生物学功能及与哮喘的关系进行简要综述。     

急性冠状动脉综合征患者辅助性T细胞9检测及其临床意义

目的 探讨辅助性T细胞9(Th9)及白细胞介素(IL)-9在急性冠状动脉综合征(ACS)患者外周血中的变化及其临床意义.方法 纳入ACS患者及健康体检者各95例,使用流式细胞术检测受试者外周血Th9比例,使用免疫酶联吸附试验(ELISA)检测血清IL-9和C反应蛋白(CRP)水平,比较Th9比例及IL-9水平在两组间的差异,同时分析它们与CRP的关系.结果 ACS患者外周血Th9细胞比例显著高于对照组[(4.31±1.02)％vs.(1.29±0.32)％,P＜0.01],IL-9水平亦显著高于对照组(6.31 ng/L vs.1.02 ng/L,P＜0.01);ACS患者血清CRP水平亦显著高于对照组(32.18 μg/ml vs.2.41 μg/ml,P＜0.01).ACS患者血清Th9比例(r=0.52,P＜0.01)及IL-9水平(r=0.46,P＜ 0.01)均与CRP呈正相关.结论 ACS患者外周血Th9比例及血清IL-9水平均高于对照组,且与CRP水平呈正相关,Th9可能参与了ACS发生发展.     

支原体肺炎患儿外周血Th9细胞及IL-9的变化及临床意义

目的探讨支原体肺炎(mycoplasma pneumoniae pneumonia,MPP)患儿外周血Th9细胞及其细胞因子IL-9水平与肺功能变化的相关性。方法选取100例MPP患儿为研究对象,依据是否合并肺部哮鸣音分为喘息组(n=58)和非喘息组(n=42),选取50例健康儿童为对照组。采用流式细胞仪检测外周血Th9细胞比例;采用Elisa法检测血清IL-9水平;采用肺功能检测仪检测75%、50%、25%肺活量最大呼气流速(V75、V50、V25),呼气高峰流量(peak expiratory flow,PEF),第1秒时间肺活量(forced expiratory volume in 1s,FEV_1%)。结果喘息组和非喘息组外周血Th9细胞及IL-9水平较对照组显著升高(P0.05);喘息组外周血Th9细胞及IL-9水平较非喘息组显著升高(P0.05)。与非喘息组相比较,喘息组PEF%、FEV_1%、V75%、V50%、V25%均显著降低(P0.05)。Pearson相关分析结果显示,MPP患儿外周血Th9细胞比例、IL-9水平与PEF%、FEV_1%、V25%、V50%、V75%呈负相关(P0.05)。结论 MPP患儿Th9细胞及IL-9表达随病情加重而增加,Th9细胞及IL-9可能是MPP诊断及转归的潜在评价指标。     

Th9与支气管哮喘

支气管哮喘(简称哮喘)是一种由多种细胞如淋巴细胞、嗜酸粒细胞、肥大细胞等及其细胞组分参与的气道慢性炎症疾患,Th2细胞被认为是哮喘发病机制中的主要效应细胞.长期以来,白介素9(IL-9)都被认为是Th2类细胞因子,在变应性疾病,尤其是过敏性哮喘、变应性鼻炎等发病机制中起着重要的作用.近年来研究发现,机体内可能存在着一群...     

醒脑静对老年急性脑出血患者Th9细胞及IL-9水平的影响

目的 探讨醒脑静对老年急性脑出血(ICH)患者外周血中辅助性T细胞-9(Th9)及血清中白细胞介素-9(IL-9)水平的影响.方法 纳入202例该院门诊及住院的老年ICH患者,随机分为两组,其中常规治疗组100例予常规治疗,醒脑静组102例予醒脑静加常规治疗,另取100例性别及年龄匹配的健康检验者作为对照.使用流式细胞术检测外周血Th9比例,使用免疫酶联吸附(ELISA)法检测血清IL-9水平；采用美国国立卫生院卒中量表(NIHSS)、蒙特利尔认知评估量表(Moca)、日常生活能力评定量表(ADL)对疗效进行评定.结果 治疗前:ICH患者外周血中Th9比例及IL-9水平均显著高于对照组(均P＜0.05)；治疗后:醒脑静组外周血Th9比例及IL-9水平下降较常规治疗组明显[Th9:(0.42±0.13)％ vs(0.54 ±0.12)％；IL-9:(0.51±0.09) pg/ml vs (0.64±0.12) pg/ml,P＜0.05]；醒脑静组对神经功能缺损的改善程度较常规治疗组更明显(P＜0.05).结论 Th9可能参与了ICH发生、发展,醒脑静可能通过减轻细胞因子介导的炎性反应对脑组织具有保护作用,从而改善ICH患者的预后.     

类风湿关节炎患者外周血辅助性T细胞9及白细胞介素-9的变化及临床意义

目的 观察类风湿关节炎(RA)患者外周血中辅助性T细胞9(Th9)及血清中白细胞介素(IL)-9的变化,探讨其与RA临床表现的相关性及其可能的免疫学发病机制.方法 收集36例RA患者和22名健康对照者,RA患者根据病情活动度不同分为病情重度活动组22例、病情中度活动组14例.流式细胞仪检测患者和健康对照者外周血中Th9细胞的变化;酶联免疫吸附试验(ELISA)检测RA患者及健康对照者血浆中IL-9等细胞因子的水平.采用t检验、Spearman相关分析进行统计学分析.结果 RA患者外周血中Th9比例显著高于健康对照组[分别为(0.99±0.50)％,(0.21±0.08)％,P＜0.01];RA患者重度活动组的Th9表达率显著高于中度活动组[分别为(1.18±0.52)％,(0.69±0.25)％,P＜0.01].RA患者外周血IL-9水平高于健康对照[分别为(1.06±0.42) pg/ml,(0.69±0.13) pg/ml,P＜0.01],重度活动组的RA患者IL-9水平[( 1.37±0.47) pg/ml]高于中度活动组[(0.94±0.30) pg/ml],差异有统计学意义(P＜0.05).RA患者外周血Th9的表达与疾病活动指数(DAS )28、红细胞沉降率(ESR)、C反应蛋白(CRP)、关节压痛数、关节肿胀数及类风湿因子(RF)滴度、IL-9的水平呈正相关;RA患者IL-9的水平与DAS28、ESR、关节压痛数、关节肿胀数呈正相关.结论 RA患者外周血Th9细胞比例及血浆中IL-9水平显著升高,且与疾病活动度及相关炎症指标明显相关,提示Th9及IL-9参与RA的发病及病情发展.     

Th9细胞分化及与炎症性肠病关系的研究进展

炎症性肠病(IBD)是一组病因复杂、机制未明的慢性非特异性自身免疫性疾病,发病与基因易感、肠道微生态失衡、肠黏膜屏障功能受损、肠道固有性和获得性免疫调节紊乱等有关.Th9细胞作为新发现的免疫细胞,被证实与多种自身免疫性疾病相关,白细胞介素-9(IL-9)是其分泌的细胞因子,针对IL-9抗体的研究可能是IBD治疗的新靶点...     

Th17细胞的生物学特性及其在寄生虫感染中的作用

辅助性T细胞传统上分为Th1型和Th2型.近年研究者发现了一种新的CD4+T细胞亚群,可以产生白细胞介素17(IL-17),被称为Th17细胞.Th17细胞在炎症反应中发挥着重要的调节作用,它的产物IL-17等与原虫、吸虫、绦虫等寄生虫感染有联系.该文就Th17细胞亚群及其产物在寄生虫感染中的作用作一简要综述.     

Medical ethics in the 21st century

OBJECTIVES: To foresee how medical ethics may develop in the 21st century. DESIGN: We have looked into our crystal ball to see what factors are likely to drive medical ethics over the next few decades. We have given examples of how such factors might affect specific issues. RESULTS: Those factors that we identified as likely to shape the future of medical ethics are: Globalization: Medical ethics is likely to have to grapple increasingly with ethical issues arising from the huge discrepancies in the level of health care available in different countries. Increase in longevity: We predict that there will be, at least amongst the richer nations, a significant increase in life expectancy. This will result in issues of resource allocation becoming increasingly problematic within medicine. Child enhancement: Developments in genetics combined with control of reproduction will make it possible to select our children for a broad range of characteristics. There are optimistic and pessimistic predictions as to how such power will be used. In either case, this area will be an important focus of concern in medical ethics. The biological determination of behaviour: Genetic research will lead to an increasing sense that undesirable behaviour is genetically determined. This will lead to a re-examination of such concepts as criminal responsibility. Therapeutic research and clinical practice: We predict that an increasing amount of clinical practice will be within the setting of clinical trials. The ethics of therapeutic research and clinical practice will need to be brought within a coherent framework.     

醋柳黄酮对大鼠心肌缺血-再灌注损伤及MMP-9表达的影响

目的观察醋柳黄酮(TFH)对大鼠心肌缺血-再灌注后损伤及组织MMP-9表达的影响,探讨对心肌缺血-再灌注损伤后保护机制。方法将50只大鼠随机分组:模型组、氯沙坦组、醋柳黄酮大、小剂量组及假手术组。结扎左冠状动脉前降支30min后松开制作心肌缺血-再灌注模型。对心肌组织进行HE染色观察心肌坏死的面积及病理变化,免疫组织化学检测再灌注心肌组织MMP-9表达。结果 HE切片观察TFH大、小剂量组预处理的大鼠心肌坏死较模型组明显减轻,免疫组化结果显示TFH大、小剂量组较模型组MMP-9表达减少,有统计学意义。结论TFH对再灌注损伤心肌有保护作用,其作用机制与抑制心肌中MMP-9表达有关。     

The educated patient: new challenges for the medical profession

The medical profession is facing significant changes in the way the rest of society relates to it. Mass education, mass media and mass consumerism have boomed in the 20th century, putting an increasing amount of pressure on professionals to meet rising public expectations. If doctors are to continue to provide a service that meets the demands of citizens and taxpayers, they need to develop a new relationship with patients, acting not as instructors but as guides, to help people make decisions about their own health. They will have to be more accountable for the quality of care they provide and work with a wider range of health and non-health professionals to meet patients' needs. Doctors need not only to accept the consumer society but also, I will argue, to encourage it. They can work to ensure that the benefits of the information revolution are felt by people excluded from consumerism because of poverty and social isolation, working to create an empowered, informed public whose members are given the best opportunity to look after their own health.     

Immunomodulation of atherosclerosis: myth and reality

Atherosclerosis is an inflammatory disease which displays features of immune activation both locally and systemically. In the present review, we discuss the evidence for immune activation in human disease and experimental models, and survey candidate antigens associated with atherosclerosis. Studies of atherosclerosis in genetic models of immunodeficiency are analysed, as well as immunomodulating therapies and immunization protocols. Based on recent research, it is concluded that immunomodulation represents an interesting approach to the development of new prevention and treatment methods for atherosclerosis.     

Meal pattern and risk factor evaluation in one-year completers of a weight reduction program for obese men - the 'Gustaf' study

OBJECTIVES: To evaluate changes in meal patterns and in obesity related risk factors after 1 year of treatment in obese men. DESIGN: Data from two 24-h dietary recalls, performed at base-line and after 1 year of treatment, were related to changes in medical risk factors. SETTING: Academic obesity unit. SUBJECTS: Sixty-three men, aged 44 (eight) years (mean [SD]) and Base-line Body Mass Index (BMI) 37.4 (4.6) kg m-2, who had completed 1 year of treatment. The men were subdivided by tertiles according to weight change: tertile I (n = 21), mean +0.3 kg, tertile II (n = 21), mean -5.8 kg and tertile III (n = 21), mean -14.2 kg. MAIN OUTCOME MEASURES: Weight loss, changes in meal patterns and in obesity related medical risk factors. RESULTS: The reported mean energy intake decreased after treatment in tertiles II and III by 700 (1300) kcal (P < 0.05) and 700 (900) kcal (P = 0.001), respectively. In tertile III the energy-% from fat decreased (P < 0.05) with a reciprocal increase in energy-% from protein (P < 0.05). The frequency of snacks of a low nutritional quality decreased (P < 0.01) in tertile III together with an increase in energy-% from 'hot meals of good quality' (P < 0.05). Obesity related risk factors (anthropometry, blood pressure, serum lipid concentrations, blood glucose and plasma insulin) improved in a beneficial way only in tertile III. CONCLUSIONS: The weight loss in the successful tertile III men was to a great extent explained by fewer low quality snacks but more energy from high quality meals. These changes reflected the behaviour modification strategy recommended.     

Clinical efficacy of the Toll-like receptor 9 agonist cobitolimod using patient-reported-outcomes defined clinical endpoints in patients with ulcerative colitis

BackgroundThe Toll-like-receptor 9 (TLR-9) agonist cobitolimod (DIMS0150, Kappaproct^®) is a promising therapeutic option for ulcerative colitis (UC) patients.AimsThe objectives of this post-hoc analysis using the COLLECT study data was to investigate the clinical effects of cobitolimod using patient-reported-outcomes (PRO) defined endpoints.MethodsDual topical administration of cobitolimod was studied in a randomised, multicentre clinical trial named COLLECT in moderate-to-severe UC patients. Symptomatic remission (SR) was studied in 104 patients based on their e-diary records and was defined as absence of blood in stool and a mean daily stool frequency (SF) < 4.ResultsSR was achieved at week 4 in 17.1% of cobitolimod vs. 5.9% of placebo treated patients (p = 0.13), at week 8 in 35.7% vs. 17.6% (p = 0.07), and at week 12 in 38.6% vs. 17.6% (p = 0.04) of the patients, respectively.SR rates with cobitolimod and placebo in anti-TNFα experienced patients were smaller but with a broadly similar relative effect-size to anti-TNFα naïve patients. Clinical efficacy was higher in patients with moderate compared to severe disease.ConclusionsApplication of the Toll-like-receptor 9 (TLR-9) agonist cobitolimod is able to induce remission as assessed by PRO measures in UC patients with moderate-to-severe activity as well as in anti-TNFα experienced and naïve patients supporting the overall efficacy of the substance.     

Targeting AMP-activated protein kinase as a novel therapeutic approach for the treatment of metabolic disorders

In the light of recent studies in humans and rodents, AMP-activated protein kinase (AMPK), a phylogenetically conserved serine/threonine protein kinase, has been described as an integrator of regulatory signals monitoring systemic and cellular energy status. AMP-activated protein kinase (AMPK) has been proposed to function as a 'fuel gauge' to monitor cellular energy status in response to nutritional environmental variations. Recently, it has been proposed that AMPK could provide a link in metabolic defects underlying progression to the metabolic syndrome. AMPK is a heterotrimeric enzyme complex consisting of a catalytic subunit and two regulatory subunits β and γ. AMPK is activated by rising AMP and falling ATP. AMP activates the system by binding to the γ subunit that triggers phosphorylation of the catalytic subunit by the upstream kinases LKB1 and CaMKKβ (calmodulin-dependent protein kinase kinase). AMPK system is a regulator of energy balance that, once activated by low energy status, switches on ATP-producing catabolic pathways (such as fatty acid oxidation and glycolysis), and switches off ATP-consuming anabolic pathways (such as lipogenesis), both by short-term effect on phosphorylation of regulatory proteins and by long-term effect on gene expression. As well as acting at the level of the individual cell, the system also regulates food intake and energy expenditure at the whole body level, in particular by mediating the effects of insulin sensitizing adipokines leptin and adiponectin. AMPK is robustly activated during skeletal muscle contraction and myocardial ischaemia playing a role in glucose transport and fatty acid oxidation. In liver, activation of AMPK results in enhanced fatty acid oxidation as well as decreased glucose production. Moreover, the AMPK system is one of the probable targets for the anti-diabetic drugs biguanides and thiazolidinediones. Thus, the relationship between AMPK activation and beneficial metabolic effects provide the rationale for the development of new therapeutic strategies in metabolic disorders.     

A review of the metabolic syndrome

While the concept of this syndrome has been described more than 60 years ago, and more formally almost 20 years ago, the controversy continues as to its utility, which of the various syndrome definitions should be used and their ability to predict diabetes and/or cardiovascular disease. The metabolic syndrome, of cardiovascular risk factors, provides an early warning of at risk subjects and emphasises the need to treat more aggressively (by at least lifestyle modification) patients with multiple abnormalities even though the abnormalities might be slight. Further, the syndrome can be easily used in clinical practice and when it is assessed against the background of the patient's age, sex and smoking habits, it provides an evaluation of potential cardiovascular risk. Prospective intervention studies are the only means of definitively accepting or refuting the usefulness of the syndrome. The metabolic syndrome is an entity which merits attention from both the medical profession and public health authorities.