Cost effectiveness of antiviral treatment with zalcitabine plus zidovudine for AIDS patients with CD4+ counts less than 300/microliters in 5 European countries

A cost-effectiveness model was developed on the basis of early clinical trial results from the US reporting sustained CD4+ cell response in patients receiving zalcitabine in addition to zidovudine. This model was then adapted and applied to 5 European countries to assess the comparative cost effectiveness of adding zalcitabine to antiviral treatment for AIDS patients. The countries included in the modelling effort were Switzerland, France, Italy, Germany and the UK. The model used a Markov state-transition process to estimate the rate of acute opportunistic disease episodes, lifetime medical treatment costs, and survival for populations of AIDS patients with baseline CD4+ counts of less than 300/microliters. Physician panels in each country developed standard treatment algorithms and adjusted the epidemiological data to reflect the AIDS profile of each country. Economic consultants provided cost data. Results from this exploratory data analysis show that if CD4+ counts correlate with the incidence of opportunistic disease episodes as expected, the combined use of zalcitabine and zidovudine for a 1-year period should be cost effective.     

艾滋病患者机会性感染与CD4^＋T细胞计数的关联分析

目的观察艾滋病患者治疗6个月内的机会性感染与CD4^＋ T细胞计数之间的关系。方法对136例患者在治疗6个月内机会性感染与CD^4＋ T细胞计数进行回顾性调查分析。结果治疗3个月内有87.5%（119/136）的患者CD4^＋ T细胞数≤200个/μl,治疗6个月内41.9%（57/136）的患者CD4^＋T细胞数≤200个/μl。初始治疗时CD4^＋ T细胞数≤200个/μl的136例中发生多种机会性感染82例,感染率为60.3%;治疗6个月时而CD4^＋ T细胞计数〉200个/μl的79例患者中,只有3例发生了机会性感染,其感染率3.8%。结论艾滋病患者在CD4^＋ T细胞数≤200个/μl时机会性感染出现频率较少,CD4^＋ T细胞数〈200个/μl〈200个/μl时机会性感染的频率明显增加;初始治疗时全部患者CD4^＋ T细胞数〈200个/μl,很容易发生各种机会性感染。     

Submerged cultivation of medicinal mushrooms: bioprocesses and products (review)

Medicinal mushrooms belonging to higher Basidiomycetes are an immensely rich yet largely untapped resource of useful, easily accessible, natural compounds with various biological activities that may promote human well-being. The medicinal properties are found in various cellular components and secondary metabolites (polysaccharides, proteins and their complexes, phenolic compounds, polyketides, triterpenoids, steroids, alkaloids, nucleotides, etc.), which have been isolated and identified from the fruiting bodies, culture mycelium, and culture broth of mushrooms. Some of these compounds have cholesterol-lowering, anti-diabetic, antioxidant, antitumor, immunomodulating, antimicrobial, and antiviral activities ready for industrial trials and further commercialization, while others are in various stages of development. Recently, the submerged cultivation of medicinal mushrooms has received a great deal of attention as a promising and reproducible alternative for the efficient production of mushroom mycelium and metabolites. Submerged cultivation of mushrooms has significant industrial potential, but its success on a commercial scale depends on increasing product yields and development of novel production systems that address the problems associated with this technique of mushroom cultivation. In spite of many researchers' efforts for the production of bioactive metabolites by mushrooms, the physiological and engineering aspects of submerged cultures are still far from being thoroughly studied. The vast majority of studies have focused on polysaccharide and ganoderic acid production in submerged cultivation of medicinal mushrooms, and very little has been written so far on the antioxidant and hemagglutinating activity of submerged mushroom cultures. The purpose of this review is to provide an update of the present state of the art and future prospects of submerged cultivation of medicinal mushrooms to produce mycelium and bioactive metabolites, and to make a contribution for the research and development of new pharmaceutical products from mushrooms. A brief overview of the metabolic diversity and bioactive compounds of mushrooms produced by submerged cultures is also given.     

外用他克莫司对寻常型银屑病患者CD4^＋CD25^＋调节性T细胞的影响

目的 探讨外用他克莫司对寻常型银屑病患者外周血CD4^＋CD25^＋调节性T细胞（CD4^＋CD25^＋Treg）的影响.方法 给予48例寻常型银屑病患者他克莫司软膏,每日2次外用,用药8周.治疗前和治疗后,用流式细胞仪检测患者外周血CD4^＋CD25^＋调节性T细胞的表达水平,并对患者进行PASI评分.结果 治疗8周后,总有效率为91.5%.治疗前,银屑病进行期、静止期患者及正常人外周血CD4^＋CD25^＋Treg与CD4＋淋巴细胞的百分比为（2.64±0.86）%、（3.98±0.96）%、（8.46±1.54）%,三者比较,差异均有极显著性（P＜0.01）;治疗后,进行期和静止期患者外周CD4^＋CD25^＋Treg与CD4＋淋巴细胞的百分比较治疗前均有明显升高（P＜0.01）,但仍低于正常人,三者比较,差异均有极显著性（P＜0.01）.结论 寻常型银屑病存在CD4^＋CD25^＋调节性T细胞异常,他克莫司可通过上调CD4^＋CD25^＋调节性T细胞来治疗寻常型银屑病.     

艾滋病患者抗病毒治疗前CD4^＋水平与死亡率的关系

目的通过临床病例分析,观测艾滋病患者抗病毒治疗前CD4^＋细胞计数水平与治疗后死亡率的关系。方法分析了30例艾滋病患者抗病毒治疗3个月内死亡率及其与治疗前CD4^＋细胞水平的对应关系。结果发现死亡患者于治疗前的CD4＋细胞计数显著低于存活患者,而CD4^＋细胞计数〈50个/mm3的患者死亡率达45%。结论CD4^＋细胞计数严重低下的艾滋病患者死亡率显著增高,提倡早期治疗,以减少死亡率,降低治疗成本。     

凉血解毒方药对原发免疫性血小板减少症患者外周血CD4＋CD2＋5调节性 T 细胞水平的影响

目的：观察原发免疫性血小板减少症（ ITP）患者治疗前后外周血CD4＋CD2＋5调节性T细胞水平变化,探讨凉血解毒方药对ITP患者CD4＋CD2＋5调节性T细胞的作用。方法选取56例ITP患者,男12例,女44例;年龄18～62岁,中位年龄29岁。给以凉血解毒方药治疗（地黄止血胶囊2‘．0 g,3次／d,口服,凉血解毒中草药煎剂升板汤,1剂／d）。患者于治疗前、治疗后90 d分别采取外周静脉血,采用流式细胞术检测CD4＋CD2＋5调节性T细胞水平。20例健康体检者为正常对照组。结果治疗后第90天,总有效率为73．2％。56例ITP患者治疗前外周血 CD4＋CD2＋5调节性T细胞表达水平低于正常对照组[（1．01±0．67）％,（2．81±0．52）％],差异有统计学意义（ P ＜0．05）;重症ITP患者CD4＋CD2＋5调节性 T细胞水平低于非重症患者[（0．71±0．23）％,（1．48±0．64）％],差异有统计学意义（ P ＜0．01）;患者治疗后90 d CD＋4 CD2＋5调节性T细胞水平高于治疗前[（1．93±0．53）％,（10．1±0．67）％],与治疗前比较差异有统计学意义（ P ＜0．05）;治疗后有效组CD4＋CD2＋5调节性T细胞水平高于无效组,差异有统计学意义（P ＜0．05）。结论 ITP 患者外周血CD 4＋CD 2＋5调节性 T 细胞水平低于正常对照组（ P ＜0．05）;凉血解毒方药提升CD4＋CD2＋5调节性T 细胞水平可能是治疗ITP的疗效机制。     

不同剂量雷帕霉素对小鼠体内CD4+CD25+Treg细胞的影响

目的研究不同剂量雷帕霉素对小鼠体内Treg细胞的影响。方法将SPF级昆明系小鼠60只随机分为对照组(A)和实验组(B、C、D),B、C、D三组分别灌胃雷帕霉素1、2、3 mg.kg-1,A组每天予以无菌水灌胃,共3周。3周后,无菌条件下心脏采血,EDTA抗凝,分离脾脏,制备单细胞悬液,采用流式细胞仪检测小鼠外周血和脾脏中CD4+CD25+调节性T细胞水平(CD4+CD25+Treg细胞占CD4+T细胞的百分比)。结果实验组(B、C、D)小鼠外周血和脾细胞中CD4+CD25+Treg细胞水平分别为(9.62±1.43)%(、13.76±1.97)%(、15.41±2.45)%和(12.23±4.56)%(、23.03±6.18)%(、25.17±6.42)%,对照组(A)小鼠外周血和脾细胞中CD4+CD25+Treg细胞水平分别为(3.52±0.65)%和(6.53±3.01)%,无论是在外周血还是脾细胞中,B、C、D组CD4+CD25+Treg细胞水平明显高于A组(P0.05),C、D组与B组之间CD4+CD25+Treg细胞水平也有明显差异性(P0.05),C组和D组之间CD4+CD25+Treg细胞水平无明显差异性(P0.05)。结论雷帕霉素能够诱导昆明系小鼠体内CD4+CD25+Treg细胞增殖,其使用剂量可以影响CD4+CD25+Treg细胞的增殖程度。     

Comparative study of hemagglutination and lectin activity in Australian medicinal mushrooms (higher Basidiomycetes)

Fifteen Australian mushroom species (higher Basidiomycetes) were assessed for hemagglutination and lectin activity. Hemagglutination activity was evaluated using both neuraminidase treated and untreated rabbit and human A, B, and O erythrocytes. Lectin activity was determined by the ability of various mono- and oligosaccharides to inhibit hemagglutination activity. Of the mushrooms evaluated, seven contained lectin activity. However, five (Agaricus bitorquis, Chlorophyllum brunneum, Coprinus comatus, Cortinarius sp. TWM 1710, and Omphalotus nidiformis) expressed lectin activity in only one of two collections tested. The two remaining lectin active mushroom species (Phlebopus marginatus and Psathyrella asperospora) possessed lectin activity with the same sugar specificity in both collections. Although lectins were identified with diverse specificity, lactose-specific lectin activity was most frequently identified, being present in Agaricus bitorquis, Copronus comatus, Omphalotus nidiformis, and Phlebopus marginatus. In contrast, Psathyrella asperospora, Cortinarius sp. TWM 1710, and Chlorophyllum brunneum were found to possess lectin activity specific for N-acetyl-D-glucosamine, galactose, and N-acetyl-neurammic acid, respectively. Significantly, the galactose-specific lectin activity identified in Cortinarius sp. TWM 1710 and the lactose-specific lectin activity in Phlebopus marginatus have not been previously reported.     

胃癌患者外周血CD4+CD25+CD127lo/-调节性T细胞的表达及意义

目的:探讨胃癌患者外周血中CD4 CD25 CD127lo/-调节性T细胞(regulatory T cells,Treg)的表达及意义。方法:采用流式细胞术检测26例胃癌患者、30例胃溃疡患者和20例健康志愿者外周血中CD4 CD25 CD127lo/-Treg、细胞毒性T细胞(cytotoxic T lympho-cytes,CTL)和NK细胞,采用ELISA法检测血清中γ-干扰素(interferon γ,IFN-γ)的表达水平。结果:胃癌患者外周血中CD4 CD25 CD127lo/-Treg占CD4 T淋巴细胞的百分比为(6.12±2.08)%,高于胃溃疡患者和健康志愿者(P均<0.05)。胃癌患者外周血中CD4 CD25 CD127lo/-Treg水平与CTL、NK细胞及IFN-γ呈负相关。结论:胃癌患者外周血中具有免疫抑制活性的CD4 CD25 CD127lo/-Treg水平较高,对胃癌患者具有肿瘤免疫抑制作用。     

免疫性血小板减少症患者外周血CD4~+CD25~+调节性T细胞变化的临床意义

目的探讨免疫性血小板减少症(ITP)患者治疗前后CD4+CD25+调节性T细胞的变化及其临床意义。方法采用流式细胞术检测62例ITP患者(A组)采用不同治疗方案治疗前后和36例正常对照者(B组)外周血CD4+CD25+调节性T细胞比例。采用RT-PCR检测Foxp3mRNA的表达。结果与B组比较,A组治疗前CD4+CD25+调节性T细胞比例较高[(9.60±4.15)%vs.(16.56±5.68)%],CD4+Foxp3+和CD4+CD25+Foxp3+调节性T细胞比例较低[(3.88±1.34)%vs.(1.98±1.53)%和(2.72±0.93)%vs.(1.38±0.98)%](P<0.05)。与治疗前比较,A组治疗后CD4+CD25+调节性T细胞比例降低[(16.56±5.68)%vs.(10.72±5.15)%](P<0.05)。利妥昔单抗联合丙种球蛋白治疗组CD4+CD25+调节性T细胞比例较其他方案治疗组升高(P<0.05)。A组治疗前的Foxp3mRNA表达低于B组,治疗后明显升高(P<0.05)。结论 CD4+CD25+调节性T细胞数量可能与ITP的严重性密切相关。     

Effect of coixenolide on CD4+ CD25+ regulatory T cell in peripheral blood of aged patients with malignant tumor

目的 探讨薏苡仁酯(coixenolide)对高龄恶性肿瘤患者外周血调节性T细胞(Treg)的作用.方法 检测30例80岁以上老年恶性肿瘤患者(肿瘤组)薏苡仁酯治疗前后外周血Treg占总CD4+T细胞比例和血IL-2 mRNA变化.结果与30例健康老年人(对照组)进行比较.结果 肿瘤组外周Treg占总CD4+T细胞比例、血IL-2 mRNA水平均明显高于对照组(P＜0.01).肿瘤组外周血Treg比例与血IL2 mRNA水平呈正相关(r=0.921,P＜0.01).肿瘤组在薏苡仁酯治疗2个周期后,外周血Treg、IL-2 mRNA水平较治疗前明显下降(P＜0.01).结论 薏苡仁酯可能通过下调IL-2分泌和Treg数目解除免疫抑制而发挥抗肿瘤作用.     

Integrin beta2-chain (CD18) over-expression on CD4+ T cells and monocytes after ischemia/reperfusion in patients undergoing primary percutaneous revascularization

beta2-integrin subunit (CD18) plays an essential role in leukocyte recruitment and adhesion in sites of endothelial injury. We analyzed the surface expression of CD18 on T lymphocytes and monocytes in a series of patients presenting acute coronary syndrome (ACS) who underwent primary percutaneous intervention (PCI) for coronary artery revascularization. We found that basal CD18 expression on peripheral blood-derived CD4+ (but not CD8+) T lymphocytes was significantly increased in ACS patients as compared with age-matched healthy volunteers. During primary PCI, a significant increase in CD18 molecule density was detected immediately after balloon deflation (reperfusion) on both CD4+ T cells and monocytes obtained from the right atrium (RT) as compared with basal values. These data suggest that upregulation of CD18 molecules plays an important role in local recruitment of CD4+ T cells and monocytes to the site of endothelial damage after ischemia/reperfusion, therefore being responsible, at least in part, for the inflammatory-mediated complications associated with primary PCI.     

慢性乙型肝炎患者外周血CD4+CD25+high调节性T细胞对免疫状态的影响

目的 探讨CD4 CD25 high调节性T(Tr)细胞在慢性乙型肝炎(CHB)患者外周血的变化及其对免疫状态的影响.方法 用流式细胞仪技术分析比较42例CHB患者及20例正常健康人外周血中CD4 CD25 highTr细胞,同时检测CD4 T细胞和CD8 T细胞.结果 与健康对照组相比,CHB组CD4 CD25 highTr细胞百分率显著升高(P＜0.05),而CD4 T细胞显著下降(P＜0.05);CD8 T细胞虽有增加趋势,但无差异(P＞0.05).CHB组CD4 CD25 highTr细胞百分率与HBV DNA载量有一定的关系,但与血清ALT水平无相关(P＞0.05).结论 CHB患者外周血CD4 CD25 highTr细胞升高可能是导致机体免疫功能下降的原因之一.     

甲泼尼龙对哮喘患者外周血CD4~+ CD25~+调节性T细胞影响的体外研究

目的观察哮喘患者外周血中CD4+ CD25+调节性T细胞(Treg)功能状态及甲泼尼龙对其的影响。方法清晨取静脉血5 mL,常规分离外周血单个核细胞,分为健康组、哮喘组及1×10-7 mol·L-1甲泼尼龙哮喘干预组,刺激培养48 h,用ELISA法测定IL-10及TGF-β1的浓度;流式细胞仪检测CD4+CD25+Treg的比例及细胞内Foxp3表达,用SPSS 17.0进行分析。结果哮喘组,外周血CD4+ CD25+ Treg细胞比例降低,CD4+ CD25+ Foxp3+ Treg细胞减少,TGF-β1分泌减少,IL-10分泌有增高趋势,但与健康组比较无统计学意义;甲泼尼龙可以明显增加哮喘急性发作期患者CD4+ CD25+ Treg比例,Foxp3表达明显增强;但未能增加TGF-β1及IL-10的分泌。结论哮喘患者CD4+ CD25+ Treg功能低下,可能是哮喘发病机制之一;甲泼尼龙可能通过上调CD4+ CD25+ Treg数量,起到控制哮喘急性发作的作用。     

来氟米特对胶原性关节炎大鼠CD4+CD25+调节性T细胞的影响

目的:探讨来氟米特对胶原性关节炎中免疫抑制性CD4+CD25+调节性T细胞的作用.方法:II型胶原诱导Wistar大鼠,建立胶原性关节炎模型;检测关节炎大鼠多发性关节炎评分,每周2次;流式细胞仪检测脾淋巴细胞中CD4+CD25+调节性T细胞的比例;RT-PCR检测脾淋巴细胞中Foxp3 mRNA的表达.结果:与模型组比...     

万古霉素负荷剂量对重症患者24小时药时曲线下面积(AUC24)的影响

目的评价万古霉素负荷剂量对重症患者血万古霉素24小时药时曲线下面积(AUC24)的影响。方法回顾分析2015年1月-2017年9月入住广州医科大学附属第二医院重症医学科的319例临床怀疑或证实存在严重的革兰阳性球菌感染的重症患者,根据医嘱中是否使用万古霉素25mg/kg体质量的负荷剂量,将患者分为普通用药组和负荷剂量组,计算万古霉素的AUC24>400为目标AUC24。通过多元线性逐步回归法和Logistic回归进行多因素分析。生存分析采用Kaplan-Meier法进行分析。结果负荷剂量组纳入患者68例,普通用药组纳入患者156例。普通用药组AUC24明显低于负荷剂量组,两者比较差异具有显著意义(P<0.001);负荷剂量和普通用药组患者住院死亡率存在差异,分别为20.59%、35.26%。将多因素纳入Logistic回归方程分析后发现,使用万古霉素负荷剂量患者的死亡率为普通用药组的47.80%。Kaplan-Meier生存分析提示两者生存曲线比较差异存在显著差异(P=0.02)。结论用万古霉素25mg/kg负荷剂量给药方案能有效提高临床怀疑或证实存在严重的革兰阳性球菌感染重症感染患者万古霉素AUC24的水平和达标率,同时降低ICU住院死亡率。     

Anti-inflammatory properties of a novel wound healing and immunomodulating agent, tetrachlorodecaoxygen complex (TCDO)

The first phase of the healing process is characterized by the development of an inflammatory reaction involving migration of inflammatory cells and release of inflammatory mediators. In a previous study, we have demonstrated that the water soluble tetrachlorodecaoxygen complex (TCDO), first synthetized to promote wound healing, inhibits polymorphonuclear (PMN) migration. The aim of the present study was to investigate the activity of TCDO on the progression of an acute non-specific inflammatory reaction, on the release of 6-keto-PGF1 alpha and PGE2 and on PMN oxidative metabolism in the rat. Injected in the pleural cavity, TCDO (15 mumoles/rat) significantly decreased the number of exudative cells while 1.5 mumoles/rat inhibited PMN oxidative metabolism ex vivo (assessed by chemiluminescent assay and measurement of O2- generation) after stimulation of the cells by opsonized zymosan. Similar observations were made in vitro after incubation of PMNs with various concentrations of TCDO (300 to 3 microM). The effect was dose-related and highly significant up to the concentration of 3 microM. In parallel, TCDO decreased the amounts of 6-keto-PGF1 alpha and PGE2 in exudates harvested 1 hour after the intrapleural injection of isologous serum. Effects were significantly different from control levels, from 1.5 to 0.03 mumoles/rat for 6-keto-PGF1 alpha and from 1.5 to 0.01 mumoles/rat for PGE2. This effect was observed when TCDO was injected at the same time or 1 hour before the isologous serum but not later. TCDO also inhibited LTB4 generation in vitro after PMN stimulation by calcium ionophore A23187, at concentrations up to 150 microM. The effects of TCDO in vivo and in vitro on rat PMN functions and inflammatory mediator release mimic certain activities of anti-inflammatory drugs. These properties may be beneficial in the very early stages of the wound healing process.     

薏苡仁酯对高龄恶性肿瘤患者Treg细胞的影响

目的探讨薏苡仁酯(coixenolide)对高龄恶性肿瘤患者外周血调节性T细胞(Treg)的作用。方法检测30例80岁以上老年恶性肿瘤患者(肿瘤组)薏苡仁酯治疗前后外周血Treg占总CD4+T细胞比例和血IL-2mRNA变化。结果与30例健康老年人(对照组)进行比较。结果肿瘤组外周Treg占总CD4+T细胞比例、血IL-2mRNA水平均明显高于对照组(P<0.01)。肿瘤组外周血Treg比例与血IL-2mRNA水平呈正相关(r=0.921,P<0.01)。肿瘤组在薏苡仁酯治疗2个周期后,外周血Treg、IL-2mRNA水平较治疗前明显下降(P<0.01)。结论薏苡仁酯可能通过下调IL-2分泌和Treg数目解除免疫抑制而发挥抗肿瘤作用。