BACKGROUND & AIMS: OBJECTIVES:To characterize the naturally occurring expanded-spectrum beta-lactamase from an Escherichia coli clinical isolate and to compare it with a wild-type beta-lactamase. METHODS:The chromosome-borne ampC genes from E. coli BER and E. coli EC2 were PCR amplified, sequenced and cloned into an expression vector. Antimicrobial susceptibilities of the parental isolate and the recombinant strains were determined by agar dilution methods. Kinetic parameters were determined from purified AmpC BER and AmpC EC2. RESULTS:AmpC BER was overexpressed in its original clinical isolate because of mutations in the promoter region of its gene at positions -42 and -18. The analysis of the ampC coding sequence revealed a 6 bp insertion when compared with the wild-type sequence leading to the tandem duplication of two alanine residues inside the H-10 helix. AmpC BER-producing recombinants were resistant to ceftazidime, had reduced susceptibility to other oxyiminocephalosporins (cefotaxime and cefepime), but had a greater susceptibility to cefoxitin when compared with the recombinant expressing the wild-type beta-lactamase AmpC EC2. The affinity of AmpC BER for cephalosporins and imipenem was increased, whereas the hydrolysis rate was decreased for all these compounds. In addition, the IC50 values of clavulanic acid and tazobactam for AmpC BER were increased. CONCLUSIONS:This work sheds new light on structure-function relationships of expanded-spectrum AmpC beta-lactamases.

背景与目标： 目的：鉴定来自大肠杆菌临床分离株的天然存在的广谱β-内酰胺酶，并将其与野生型β-内酰胺酶进行比较。
方法：PCR扩增来自大肠杆菌BER和大肠杆菌EC2的染色体传播的ampC基因，测序并克隆到表达载体中。通过琼脂稀释法测定亲本分离株和重组菌株的抗药性。动力学参数由纯化的AmpC BER和AmpC EC2确定。
结果：AmpC BER在其原始临床分离株中过表达，因为其基因的启动子区域位于-42和-18位。 ampC编码序列的分析显示，与野生型序列相比，插入了6 bp，导致H-10螺旋内部两个丙氨酸残基串联重复。与表达野生型β-内酰胺酶AmpC EC2的重组体相比，产生AmpC BER的重组体对头孢他啶具有抗性，对其他氧亚氨基头孢菌素（头孢噻肟和头孢吡肟）的敏感性降低，但对头孢西丁的敏感性更高。 AmpC BER对头孢菌素和亚胺培南的亲和力增加，而所有这些化合物的水解速率均降低。此外，棒酸和他唑巴坦对AmpC BER的IC50值增加。
结论：这项工作为广谱AmpCβ-内酰胺酶的结构-功能关系提供了新的思路。

BACKGROUND & AIMS: :Germinal centers (GCs) support high-affinity, long-lived humoral immunity. How memory B cells develop in GCs is not clear. Through the use of a cell-cycle-reporting system, we identified GC-derived memory precursor cells (GC-MP cells) that had quit cycling and reached G0 phase while in the GC, exhibited memory-associated phenotypes with signs of affinity maturation and localized toward the GC border. After being transferred into adoptive hosts, GC-MP cells reconstituted a secondary response like genuine memory B cells. GC-MP cells expressed the interleukin 9 (IL-9) receptor and responded to IL-9. Acute treatment with IL-9 or antibody to IL-9 accelerated or retarded the positioning of GC-MP cells toward the GC edge and exit from the GC, and enhanced or inhibited the development of memory B cells, which required B cell-intrinsic responsiveness to IL-9. Follicular helper T cells (TFH cells) produced IL-9, and deletion of IL-9 from T cells or, more specifically, from GC TFH cells led to impaired memory formation of B cells. Therefore, the GC development of memory B cells is promoted by TFH cell-derived IL-9.

背景与目标： ：生殖器中心（GC）支持高亲和力，长寿命的体液免疫。尚不清楚GC中记忆B细胞如何发育。通过使用细胞周期报告系统，我们确定了GC衍生的记忆前体细胞（GC-MP细胞）已经退出循环并达到G0期，而在GC中则表现出与记忆相关的表型，并伴有亲和力成熟和定位于GC边界。在被转移到过继宿主中之后，GC-MP细胞像真正的记忆B细胞一样重新构成了次级反应。 GC-MP细胞表达白介素9（IL-9）受体并对IL-9作出反应。用IL-9或IL-9抗体进行的急性治疗可加速或延迟GC-MP细胞向GC边缘定位并从GC退出，并增强或抑制记忆B细胞的发育，这需要B细胞内在的响应能力IL-9。卵泡辅助性T细胞（TFH细胞）产生IL-9，T细胞或更具体地从GC TFH细胞中删除IL-9导致B细胞记忆形成受损。因此，源自TFH细胞的IL-9促进了记忆B细胞的GC发育。

BACKGROUND & AIMS: BACKGROUND:Time trade-off (TTO) exercises typically present respondents with a limited time horizon, for example 10 years, thus implicitly considerably reducing remaining life expectancy for the average respondent. It is unclear how this affects health state valuations. AIM:The aim of the study is to investigate how awareness of the reduced life span implied by a 10-year TTO affects health state valuations, using an experimental design. METHODS:Two Web-based questionnaires (Q1 and Q2) were administered in a sample representative of the Dutch population. Both questionnaires contained three 10-year TTO exercises valuing three distinct health states, specified using the EQ-5D. Q1 used a TTO instruction not explicitly emphasizing the fact that remaining life expectancy was reduced to 10 years, while in Q2 respondents were explicitly made aware of this fact by emphasizing their implied age of death. Respondents answering Q1 were asked retrospectively whether they had been aware of their reduced life span due to the 10-year TTO. RESULTS:In total, 656 respondents completed the questionnaires (Q1: 339 and Q2: 317). The average age of the respondents was 43 years and 51 % of respondents were male. The average numbers of years traded off for the respondents of Q1 were for TTO1 0.443, TTO2 0.552, and TTO3 2.083 years. For the respondents of Q2, these averages were lower, i.e., TTO1 0.401 (p = 0.085 vs. Q1), TTO2: 0.546 (p = 0.036 vs. Q1), and TTO3: 1.467 years (p = 0.000 vs. Q1). Fifty-seven percent of respondents in Q1 confirmed that they were aware of the reduced life span. This spontaneous awareness had a limited and mixed influence on results. The generalized negative binomial regression analysis, explaining the time traded off showed that age, subjective life expectancy, and questionnaire Q2 (vs. Q1) were negatively associated with the years traded off, whereas education and worse health states in the TTO exercise had a significant positive impact on the years traded off. The probit model investigating the impact on the willingness to trade showed that age (-), education (+), subjective life expectancy (-), questionnaire Q2 versus Q1 (-), the interaction between Q2 and male gender (+), and worse health states in the TTO exercise (+) had a significant impact on the willingness to trade. CONCLUSION:These findings emphasize the importance of expected and implied life expectancy in TTOs.

背景与目标： 背景：时间权衡（TTO）练习通常为受访者提供有限的时间范围（例如10年），从而隐含地大大降低了平均受访者的剩余预期寿命。目前尚不清楚这如何影响健康状况评估。
目的：该研究的目的是使用实验设计，调查对10年TTO所隐含的寿命缩短的认识如何影响健康状况评估。
方法：在代表荷兰人口的样本中进行了两份基于Web的问卷（Q1和Q2）。两份问卷均包含三个为期10年的TTO演习，评估了使用EQ-5D指定的三种不同的健康状态。第一季度使用的是TTO指令，没有明确强调预期寿命会缩短至10年，而第二季度的受访者则通过强调其隐性死亡年龄来明确意识到这一事实。回顾性地回答了回答第一季度的受访者，他们是否知道由于10年的TTO而缩短了寿命。
结果：共有656名受访者完成了问卷（第一季度：339；第二季度：317）。受访者的平均年龄为43岁，而51％的受访者为男性。第一季度受访者需要权衡的平均年数为TTO1 0.443，TTO2 0.552和TTO3 2.083年。对于第二季度的受访者来说，这些平均值较低，即TTO1 0.401（p = 0.085 vs.Q1），TTO2：0.546（p = 0.036 vs.Q1）和TTO3：1.467年（p = 0.000 vs.Q1）。第一季度有57％的受访者确认他们知道寿命缩短了。这种自发的意识对结果的影响有限而又复杂。广义负二项式回归分析解释了折衷的时间，表明年龄，主观预期寿命和问卷Q2（相对于Q1）与折衷的年负相关，而TTO锻炼中的教育程度和健康状况较差对折中年的积极影响。概率模型对贸易意愿的影响进行了调查，结果显示年龄（-），教育程度（），主观预期寿命（-），调查问卷Q2与Q1（-），Q2与男性之间的相互作用（）和健康状况较差TTO演习中的州（）对贸易意愿产生了重大影响。
结论：这些发现强调了预期和隐含的预期寿命在TTO中的重要性。

BACKGROUND & AIMS: :hCAP-18/LL-37 is an antimicrobial peptide that is mainly expressed in epithelial cells. Gingival epithelial cells play pivotal roles in antimicrobial defense by expressing hCAP-18/LL-37. Porphyromonas gingivalis is a primary pathogen for chronic periodontitis and produces cysteine proteinase gingipains, which induce proinflammatory cytokines production, leading to enhance inflammatory responses. In contrast, gingipains attenuate immune responses, leading to induce anti-inflammatory responses. In this study, we investigated the ability of gingipains to attenuate P. gingivalis-induced hCAP-18/LL-37 production by human gingival epithelial Ca9-22 cells. The expression of LL-37 mRNA was increased by the infection of Ca9-22 cells with a P. gingivalis gingipains-null mutant KDP136 compared with P. gingivalis wild-type strain ATCC 33277. Interleukin (IL)-33 is involved in the development of chronic inflammatory diseases, and P. gingivalis infection increases IL-33 production by human gingival epithelial cells. P. gingivalis-induced LL-37 mRNA expression was augmented in IL-33 small interfering RNA-transfected Ca9-22 cells. Maxacalcitol (22-oxacalcitriol: OCT) is a biologically active metabolite of vitamin D3 analog, and OCT increases hCAP-18/LL-37 production by human gingival epithelial cells. The increasing expression of LL-37 mRNA by OCT was down-regulated by infection of the cells with P. gingivalis ATCC 33277 in Ca9-22 cells. Furthermore, P. gingivalis infection induced IL-33 mRNA expression in Ca9-22 cells; therefore, P. gingivalis-induced endogenous IL-33 down-regulated hCAP-18/LL-37 production by the bacterium. These findings suggested that endogenous IL-33 down-regulates the induction of hCAP-18/LL-37 production in human gingival epithelial cells.

背景与目标： ：hCAP-18 / LL-37是一种抗菌肽，主要在上皮细胞中表达。牙龈上皮细胞通过表达hCAP-18 / LL-37在抗菌防御中起关键作用。牙龈卟啉单胞菌是慢性牙周炎的主要病原体，并产生半胱氨酸蛋白酶齿龈蛋白酶，从而诱导促炎细胞因子的产生，从而增强炎症反应。相反，姜黄素减弱免疫反应，导致诱导抗炎反应。在这项研究中，我们调查了牙龈蛋白酶减弱人牙龈上皮Ca9-22细胞对牙龈卟啉单胞菌诱导的hCAP-18 / LL-37产生的能力。与齿龈假单胞菌野生型菌株ATCC 33277相比，齿龈假单胞菌齿龈蛋白酶空突变体KDP136感染Ca9-22细胞可增加LL-37 mRNA的表达。白介素（IL）-33参与了发育慢性炎症性疾病和牙龈卟啉单胞菌感染会增加人牙龈上皮细胞产生IL-33的数量。在IL-33小干扰RNA转染的Ca9-22细胞中，牙龈卟啉单胞菌诱导的LL-37 mRNA表达增加。 Maxacalcitol（22-oxacalcitriol：OCT）是维生素D3类似物的生物活性代谢产物，OCT可增加人牙龈上皮细胞产生的hCAP-18 / LL-37。通过OCT LL-37 mRNA的表达增加被Ca9-22细胞中牙龈卟啉单胞菌ATCC 33277感染的细胞下调。此外，牙龈卟啉单胞菌感染诱导Ca9-22细胞中IL-33 mRNA表达。因此，牙龈卟啉单胞菌诱导的内源性IL-33下调了细菌的hCAP-18 / LL-37产生。这些发现表明内源性IL-33下调人牙龈上皮细胞中hCAP-18 / LL-37产生的诱导。

BACKGROUND & AIMS: :This study was designed to measure symptoms, IL-4, IL-5, IFN-gamma, and eosinophilic cationic protein (ECP) in nasal secretions from subjects experiencing an artificial allergy season and to look for evidence of priming. Clinically relevant allergen was administered intranasally out of season to 12 asymptomatic individuals with seasonal allergic rhinitis. These individuals were then randomized to receive allergen or saline daily for the next 7 days. Nasal secretions and scrapings of nasal epithelium were obtained at baseline (day 1), 24 hours after the initial allergen administration (day 2), and 24 hours after the last instillation of allergen or saline (day 9). Nasal symptom scores (p < 0.0002), IL-5 mRNA (p = 0.03), and ECP (p < 0.02) increased after receiving the first challenge (day 2 compared with day 1). In the six subjects randomized to receive seven sequential daily challenges with allergen, symptom scores remained elevated (p < 0.02), IL-5 protein increased (p = 0.02), and IFN-gamma (p = 0.02) levels decreased (day 9 compared with day 1). In the six subjects randomized to receive seven sequential daily challenges with placebo, symptom scores, IL-5, and IFN-gamma levels were not significantly different (day 9 compared with day 1). Compared with the findings at day 2 (n = 12), the treated subjects (n = 6) had no further increase in symptoms but did show a further increase in IL-5 (p = 0.01) and a decrease in IFN-gamma (p = 0.02) at day 9. Daily instillation of moderate doses of allergen intranasally is characterized by persistent symptoms, elevation of IL-5, and reduced levels of IFN-gamma.

背景与目标： ：本研究旨在测量经历了人工过敏季节的受试者的鼻分泌物中的症状，IL-4，IL-5，IFN-γ和嗜酸性阳离子蛋白（ECP），并寻找引发的证据。临床相关的变应原是在季节外鼻内给予12例季节性变应性鼻炎的无症状个体。然后将这些个体随机分组，在接下来的7天中每天接受过敏原或生理盐水。在基线（第1天），首次施用过敏原后24小时（第2天）和最后滴入过敏原或生理盐水后第24小时（第9天）获得鼻腔分泌物和鼻上皮的刮痕。接受首次攻击后（第2天与第1天相比），鼻症状评分（p <0.0002），IL-5 mRNA（p = 0.03）和ECP（p <0.02）升高。在随机接受每日7次连续性过敏原攻击的6名受试者中，症状评分保持升高（p <0.02），IL-5蛋白升高（p = 0.02），IFN-γ（p = 0.02）水平降低（比较第9天）与第1天）。在随机接受安慰剂的七个连续每日挑战的六名受试者中，症状评分，IL-5和IFN-γ水平无显着差异（第9天与第1天相比）。与第2天的结果（n = 12）相比，接受治疗的受试者（n = 6）的症状没有进一步增加，但确实表现出IL-5进一步增加（p = 0.01）和IFN-γ降低（ p = 0.02）在第9天。鼻内每日滴入中等剂量的过敏原的特征是持续症状，IL-5升高和IFN-γ水平降低。

BACKGROUND & AIMS: :The key component in the so-called EPRI effective dose equivalent (EDE) methodology is an algorithm that utilizes two dosimeters (instead of multiple dosimeters) to predict the EDE for external photon exposures. The exposure scenarios that were previously studied in deriving the algorithm include parallel photon beams and point sources 33 cm from the body surface. The motivation for this study was the need to investigate source locations within 33 cm from the body so the method is more widely applicable. The ORNL stylized mathematical human phantoms and the MCNP code were used to calculate organ doses in this study. This paper presents the EDE data for point gamma sources at 0.3, 1.0, and 1.5 MeV, respectively, which are located at 10 cm from the surface of the body. The results and analyses show that the locations ranging from the overhead to the foot have resulted in conservative ratios except for two general regions near the front upper thigh and directly overhead. If all locations considered in this study were averaged for each photon energy, the overall ratio is on the conservative side. These data suggest that the EPRI EDE methodology is still valid for sources located 10 cm from the body, although the chance for resulting in a non-conservative estimate of the EDE has increased in comparison with the sources located at 30 cm from the body. Finally, this paper provides recommendations on how to apply the EPRI EDE methodology.

背景与目标： ：所谓的EPRI有效剂量当量（EDE）方法中的关键组件是一种算法，该算法利用两个剂量计（而不是多个剂量计）来预测外部光子暴露的EDE。先前在推导算法时曾研究过的曝光场景包括平行光子束和距体表33 cm的点光源。这项研究的动机是需要调查距人体33厘米以内的放射源位置，因此该方法更广泛地适用。在本研究中，使用了ORNL程式化的数学人体模型和MCNP代码来计算器官剂量。本文介绍了分别位于距人体表面10 cm处的0.3 MeV，1.0 MeV和1.5 MeV的点伽马源的EDE数据。结果和分析表明，从头顶到脚的位置范围导致了保守的比率，除了大腿前上方和直接头顶附近的两个一般区域。如果在本研究中考虑的所有位置均针对每种光子能量求平均值，则总体比率处于保守的一面。这些数据表明，EPRI EDE方法对于距离人体10厘米处的放射源仍然有效，尽管与位于人体30厘米处的放射源相比，导致EDE非保守估计的机会有所增加。最后，本文提供了有关如何应用EPRI EDE方法的建议。

BACKGROUND & AIMS: :The influence of an immunosuppressive cytokine, interleukin-10 (IL-10), on the outcome of hepatitis C virus (HCV) infection has been increasingly reported recently. A number of polymorphisms appear to control the level of IL-10 production. Among them, -592C/A, -819C/T and -1082G/A in the IL-10 gene are three most studied single nucleotide polymorphisms. To provide a more definitive conclusion about their association with the risk of HCV infection, a meta-analysis was performed by combining and summarizing a total of 17 studies. A biological justification for the choice of genetic model was provided. The results indicated no significant association between these IL-10 polymorphisms and the susceptibility to HCV infection [-592C/A: odds ratio (OR) 0.99, 95% confidence interval (CI) 0.78-1.25; -819C/T: OR 0.90, 95% CI 0.69-1.18; -1082G/A: OR 1.34, 95% CI 0.90-2.00]. However, this analysis did not account for the possible risk modifications by other factors, such as ethnicity and virus persistence. Therefore, the effects of ethnicity and virus persistence were investigated using Bayesian meta-regression and subgroup analysis. Finally, an extended case-control association study was conducted in a Chinese population involving 1140 subjects. Both serum level and genotype data of IL-10 -1082G/A were determined. As a result, a low prevalence of G allele was observed. Significantly higher IL-10 production was observed in HCV patients, especially patients with the GG genotype.

背景与目标： 免疫抑制细胞因子白介素10（IL-10）对丙型肝炎病毒（HCV）感染结局的影响最近已有报道。许多多态性似乎可以控制IL-10的产生水平。其中，IL-10基因中的-592C / A，-819C / T和-1082G / A是三个研究最多的单核苷酸多态性。为了提供关于它们与HCV感染风险之间关系的更明确的结论，通过合并和总结总共17项研究进行了荟萃分析。提供了选择遗传模型的生物学依据。结果表明，这些IL-10多态性与HCV感染的易感性之间没有显着相关性[-592C / A：优势比（OR）0.99，95％置信区间（CI）0.78-1.25； -819C / T：OR 0.90，95％CI 0.69-1.18； -1082G / A：OR 1.34，95％CI 0.90-2.00]。但是，此分析未考虑其他因素（例如种族和病毒持久性）可能造成的风险调整。因此，使用贝叶斯元回归和亚组分析研究了种族和病毒持久性的影响。最后，在一个涉及1140名受试者的中国人群中进行了扩展的病例对照研究。测定IL-10 -1082G / A的血清水平和基因型数据。结果，观察到G等位基因的低流行。在HCV患者中，尤其是具有GG基因型的患者中，IL-10的产生明显增加。

BACKGROUND & AIMS: :The septic shock-induced decrease in mesenteric blood flow and release of proinflammatory cytokines are among the major pathophysiologic changes presumed to lead to multiple organ dysfunction syndrome (MODS). Increased nitric oxide (NO) levels are associated with both decreased mesenteric blood flow and positive modulation of proinflammatory cytokine release. In this study we aimed to determine the effect of the timing of the inhibition of nitric oxide synthase (NOS) on mesenteric blood flow and serum interleukin-10 (IL-10) concentrations during endotoxin shock. A nonspecific NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME), a specific NOS inhibitor aminoguanidine (AG), or placebo were injected 20 minutes before or 20 minutes after a lipopolysaccharide (LPS) or placebo challenge to Swiss-albino mice, as pretreatment or posttreatment, respectively. At 120 minutes after LPS or placebo injection the mesenteric blood flow was measured, and blood samples from the heart were obtained for IL-10 levels in both groups. Pretreatment and posttreatment with both NOS inhibitors prevented the LPS-induced decrease in mesenteric blood flow. Pretreatment was more effective for this purpose. Pretreatment accentuated the LPS-induced increase in serum IL-10 concentrations, whereas posttreatment had no significant effect. We conclude that the timing of NOS inhibition is important for attenuating some deleterious effects of endotoxin.

背景与目标： ：败血性休克引起的肠系膜血流量减少和促炎性细胞因子释放是导致多器官功能障碍综合症（MODS）的主要病理生理变化之一。一氧化氮（NO）水平升高与肠系膜血流量减少以及促炎性细胞因子释放的正调节有关。在这项研究中，我们旨在确定内毒素休克期间一氧化氮合酶（NOS）抑制时机对肠系膜血流和血清白介素10（IL-10）浓度的影响。在脂多糖（LPS）或安慰剂攻击Swiss-20之前或之后20分钟注射非特异性NOS抑制剂NG-硝基-L-精氨酸甲酯（L-NAME），特异性NOS抑制剂氨基胍（AG）或安慰剂。白化病小鼠，分别作为预处理或后处理。在LPS或安慰剂注射后120分钟，测量肠系膜的血流量，并从心脏的血液样品中获得两组中的IL-10水平。两种NOS抑制剂的预处理和后处理均防止了LPS诱导的肠系膜血流量的减少。为此目的，预处理更为有效。预处理加重了LPS诱导的血清IL-10浓度的增加，而后处理则无明显影响。我们得出结论，抑制NOS的时机对于减弱内毒素的某些有害作用很重要。

BACKGROUND & AIMS: :The aim of study was to examine relationship among levels of cytokines (IL-6, IL-13, IL-15, TNF-α) and chemokine (IL-8), production of autoantibodies, radiographic progression, and factors describing rheumatoid arthritis (RA). A total of 156 RA patients according to ACR criteria, and 55 control subjects were recruited into study. We observed higher levels of IL-15 within RA patients compared to healthy controls. Correlations among cytokine levels and the measures of rheumatoid factors, anti-CCP, measures of disease activity, and radiographic progression were observed. We conclude that IL-15 level in circulation could serve as one of the biomarkers for RA detection.

背景与目标： ：研究的目的是检查细胞因子（IL-6，IL-13，IL-15，TNF-α）和趋化因子（IL-8）水平，自身抗体的产生，放射学进展以及描述类风湿性关节炎的因素之间的关系（RA）。根据ACR标准，共有156名RA患者和55名对照受试者被招募入研究。与健康对照组相比，我们观察到RA患者中IL-15的水平更高。观察到细胞因子水平与类风湿因子，抗CCP，疾病活动性和放射学进展程度之间的相关性。我们得出结论，循环中IL-15的水平可以作为RA检测的生物标志物之一。

BACKGROUND & AIMS: :This study aimed to highlight the importance of routine screening for hyperglycemia and to develop a standardized, evidence-based approach for the management of pemphigus patients on prolonged systemic corticosteroid (CS) therapy. A cross-sectional study was conducted in two university-affiliated teaching hospitals using a referred sample of 200 patients with a confirmed diagnosis of pemphigus vulgaris, pemphigus foliaceus, or mucous membrane pemphigoid. All patients were receiving systemic CS therapy. A total of 150 patients responded to the survey. Six participants were excluded and 144 were included. The main outcome measure was blood glucose level to detect hyperglycemia. New-onset hyperglycemia was identified in 40% of patients who received CS therapy. None of the expected variables, including age, body mass index, family history of diabetes, corticosteroid dose, and duration of corticosteroid therapy, were independently associated with new-onset hyperglycemia. These findings indicate that the prevalence of CS-induced hyperglycemia in pemphigus patients is 40% and that in patients with pemphigus or MMP, CS therapy is associated with a markedly increased risk for hyperglycemia (odds ratio = 10.7, 95% confidence interval 1.38-83.50) compared with that of patients with the same diseases who do not receive CS therapy.

背景与目标： ：这项研究的目的是强调常规筛查高血糖的重要性，并开发一种标准化的，循证的方法来治疗天疱疮患者，以延长的全身性皮质类固醇（CS）治疗。在两所大学附属教学医院中进行了一项横断面研究，使用了200名患者的参考样本，这些患者被确诊为寻常型天疱疮，叶天疱疮或粘膜天疱疮。所有患者均接受全身CS治疗。共有150位患者对此调查做出了回应。六名参与者被排除在外，其中包括144名。主要结果指标是检测高血糖的血糖水平。在接受CS治疗的患者中，有40％发现了新发的高血糖症。新出现的高血糖症与年龄，体重指数，糖尿病家族史，糖皮质激素剂量和糖皮质激素治疗持续时间等预期变量均无关。这些发现表明，天疱疮患者中CS引起的高血糖的患病率为40％，天疱疮或MMP患者中，CS治疗与高血糖的风险显着相关（优势比= 10.7，95％置信区间1.38-83.50 ）与没有接受CS治疗的相同疾病的患者相比。

BACKGROUND & AIMS: CONCLUSION:The deficient regulatory T cells may play a role in the development of allergic rhinitis. OBJECTIVE:A subpopulation of regulatory T cell that produce IL-17a were proved to show an apparent duality of regulatory T cell and effector T helper-17 cells. We studied this subpopulation in patients with allergic rhinitis. METHODS:Fresh whole blood from 20 patients with allergic rhinitis and 19 healthy donors was used to investigate the frequencies of CD4(+)IFN-γ(+) T cells (effector T helper-1), CD4(+)IL-4(+) T cells (effector T helper-2) and CD4(+)IL-17a(+) T cells (effector T helper-17) by flow cytometry after stimulation for 4-6 h. Simultaneously, CD4(+) T lymphocytes were isolated from peripheral blood mononuclear cells and then the frequencies of regulatory T cells and IL-17a-producing regulatory T cells in the allergic rhinitis group were compared with healthy controls after T-cell antigen receptor stimulation for 48 h. The suppressive capacity of CD4(+)CD25(high)CD127(low) regulatory T cells that were stimulated by Dermatophagoides pteronyssinus in both groups was isolated and assessed. RESULTS:The frequencies of effector T helper-17 and effector T helper-2 cells were higher in the allergic group compared with healthy controls. Regulatory T cells were similar in both groups, but IL-17a-producing regulatory T cells were increased in the allergic group. In addition, the capacity of regulatory T cells to suppress effector T helper-17 cytokine production was significantly decreased in the allergic group.

背景与目标： 结论：调节性T细胞的缺乏可能与过敏性鼻炎的发展有关。
目的：证明产生IL-17a的调节性T细胞亚群显示出调节性T细胞和效应T辅助细胞17的明显双重性。我们研究了变应性鼻炎患者的这一亚群。
方法：采用20例变应性鼻炎患者和19名健康供体的新鲜全血来研究CD4（）IFN-γ（）T细胞（T辅助细胞-1），CD4（IL-4）T细胞的频率。刺激4-6小时后，通过流式细胞术检测（T细胞辅助2）和CD4（）IL-17a（）T细胞（T细胞辅助17）。同时，从外周血单个核细胞中分离出CD4（）T淋巴细胞，然后在刺激48次T细胞抗原受体后，将变应性鼻炎组中调节性T细胞和产生IL-17a的调节性T细胞的频率与健康对照进行比较。 H。分离并评估了由Dermatophagoides pteronyssinus刺激的两组CD4（）CD25（高）CD127（低）调节性T细胞的抑制能力。
结果：与健康对照组相比，过敏组的效应T辅助细胞17和效应T辅助细胞2的频率更高。两组中的调节性T细胞相似，但在过敏组中产生IL-17a的调节性T细胞增加。此外，在过敏组中调节性T细胞抑制效应性T辅助17细胞因子产生的能力显着降低。

BACKGROUND & AIMS: :Background: Neuroinflammation is an important feature of epileptogenesis.Objectives: To investigate the association of Interleukin-1beta-31 (IL-1β-31) and Interleukin-1 receptor antagonist (IL1-RA) genetic polymorphisms with idiopathic generalized epilepsy and demonstrate their influence on drug resistance in children.Materials and Methods: One hundred children with idiopathic generalized epilepsy were age and gender-matched with apparently healthy controls. Both groups were genotyped for IL-1β-31, and IL1-RA gene variants, analysis of these single nucleotide polymorphisms (SNPs) was done through restriction digestion of the corresponding polymerase chain reaction (PCR) products by restriction fragment length polymorphism (RFLP) assay.Results: Genotype frequency of rs1143627 TT of IL-1β-31 and the homozygous IL1RN*I were found to be more prevalent in epileptic patients (p < .05, OR 0.12 and 5.27respectively). Also observed, T allele of IL-1β-31 and IL1-RAI/I were substantially positively correlated with drug resistance against those who responded well to antiepileptic drugs (AEDs).Conclusions: The significant association with IL-1β-31T and IL1-RAN*I alleles potentiated their useful role as predictive markers for the development of epilepsy and response to medical therapy.

背景与目标： 目的：探讨白细胞介素-1β-31（IL-1β-31）和白细胞介素-1受体拮抗剂（IL1-RA）遗传多态性与特发性全身性癫痫的关系，并证明它们的关系。材料和方法：100名特发性全身性癫痫患儿的年龄和性别与明显健康的对照组相匹配。两组均针对IL-1β-31和IL1-RA基因变异进行基因分型，通过限制性片段长度多态性（RFLP）限制性消化相应的聚合酶链反应（PCR）产物，对这些单核苷酸多态性（SNP）进行分析。结果：发现IL-1β-31的rs1143627 TT和纯合的IL1RN * I的基因型频率在癫痫患者中更为普遍（p <0.05，OR = 0.12和5.27）。还观察到，IL-1β-31和IL1-RAI / I的T等位基因与对抗癫痫药物（AED）反应良好的患者的耐药性呈正相关。结论：与IL-1β-31T和IL1-的显着相关性RAN * I等位基因增强了其作为癫痫发展和药物治疗反应的预测标志物的有用作用。

BACKGROUND & AIMS: BACKGROUND:We previously demonstrated angiotensin converting enzymes (ACE) over-expression in a dextran-sodium sulfate colitis model; ACE inhibitor (ACE-I) treatment reduced colitis severity in this model. However, ACE-I has not been tested in more immunologically relevant colitis models. AIM:We hypothesized that ACE-I would decrease disease severity in an IL-10 knockout (-/-) colitis model. METHODS:Colitis was induced by giving 10-week old IL-10-/- mice piroxicam (P.O.) for 14 days. The ACE-I enalaprilat was given transanally at a dose of 6.25 mg/kg for 21 days. Prednisolone (PSL) with or without enalaprilat were used as therapeutic, comparative groups. All groups were compared to a placebo treated group. Outcome measures were clinical course, histology, abundance of pro-inflammatory cytokines/chemokines, and epithelial barrier function. RESULTS:Enalaprilat exhibited better survival (91 %) versus other treatment groups (PSL: 85.7 %, PSL + ACE-I: 71.4 %, placebo: 66.6 %). The ACE-I and PSL + ACE-I groups showed significantly better histological scores versus placebo mice. ACE-I and the PSL groups significantly reduced several pro-inflammatory cytokines versus placebo mice. FITC-dextran permeability was reduced in the ACE-I and PSL + ACE-I groups. Blood pressure was not affected in ACE-I treated mice compared to placebo mice. CONCLUSIONS:ACE-I was effective in reducing severity of colitis in an IL-10-/- model. The addition of prednisolone minimally augmented this effect. The findings suggest that appropriately dosed ACE-I with or without steroids may be a new therapeutic agent for colitis.

背景与目标： 背景：我们先前证明了在葡聚糖-硫酸钠结肠炎模型中血管紧张素转化酶（ACE）的过度表达。在该模型中，ACEI（ACE-I）抑制剂治疗可降低结肠炎的严重程度。但是，尚未在更具免疫学意义的结肠炎模型中测试ACE-1。
目的：我们假设ACE-1可以降低IL-10基因敲除（-/-）结肠炎模型中的疾病严重程度。
方法：通过给予10周龄的IL-10-/-小鼠吡罗昔康（P.O.）14天来诱发结肠炎。 ACE-1依那普利拉经鼻给药，剂量为6.25 mg / kg，持续21天。泼尼松龙（PSL）有或没有恩那普利拉被用作治疗性比较组。将所有组与安慰剂治疗组进行比较。结果指标包括临床病程，组织学，促炎细胞因子/趋化因子的含量以及上皮屏障功能。
结果：依那普利拉的生存率（91％）优于其他治疗组（PSL：85.7％，PSL ACE-1：71.4％，安慰剂：66.6％）。与安慰剂小鼠相比，ACE-1和PSL ACE-1组的组织学评分明显更高。与安慰剂小鼠相比，ACE-1和PSL组显着减少了几种促炎性细胞因子。在ACE-I和PSL ACE-I组中，FITC-葡聚糖的通透性降低。与安慰剂小鼠相比，ACE-1治疗的小鼠的血压没有受到影响。
结论：ACE-1在降低IL-10-/-模型中结肠炎的严重程度方面有效。泼尼松龙的添加最小程度地增强了这种作用。研究结果表明，适当剂量的ACE-I与或不与类固醇激素可能是结肠炎的一种新的治疗剂。

BACKGROUND & AIMS: :Huangshui (HS), the by-product of Chinese Baijiu, has attracted considerable attention due to its nutrient and microbial composition; however, none of the studies has explored the polysaccharides in HS yet. Here, from HS, we isolated a novel polysaccharide, HSP-3, with an average molecular weight of 26.40 kDa. The structure was elucidated based on monosaccharide composition and methylation analysis, NMR, FT-IR, and AFM analysis. It is mainly composed of mannose (46.6%), galactose (17.3%), arabinose (11.2%), glucose (10.5%), xylose (8.2%), fucose (5.2%), and rhamnose (1.0%). The backbone of HSP-3 was made up of → 2)-β-d-Manp-(1 → 2,6)-β-d-Manp-(1 → 6)-β-d-Galp-(1 → 3,6)-β-d-Galp-(1 → 4)-α-l-Rhap-(1 → 3,4)-α-l-Rhap-(1 → . Moreover, stimulation of the production of ROS, NO, TNF-α and IL-6, upregulation of the mRNA and protein expression levels of TNF-α and IL-6 in THP-1 cells, and enhanced the pinocytic and phagocytic capacities of THP-1 cells exhibited significant immunomodulatory properties of HSP-3. Altogether, this study suggests that HSP-3 could be used as an active component in functional foods.

背景与目标： ：白酒的副产品hui水（HS）由于其营养成分和微生物成分而备受关注。然而，尚无研究探讨HS中的多糖。在这里，我们从HS分离出一种新型多糖HSP-3，其平均分子量为26.40 kDa。根据单糖组成和甲基化分析，NMR，FT-IR和AFM分析阐明了结构。它主要由甘露糖（46.6％），半乳糖（17.3％），阿拉伯糖（11.2％），葡萄糖（10.5％），木糖（8.2％），岩藻糖（5.2％）和鼠李糖（1.0％）组成。 HSP-3的骨架由→2）-β-d-Manp-（1→2,6）-β-d-Manp-（1→6）-β-d-Galp-（1→3组成，6）-β-d-Galp-（1→4）-α-l-Rhap-（1→3,4）-α-l-Rhap-（1→ ，TNF-α和IL-6，THP-1细胞中TNF-α和IL-6的mRNA和蛋白表达水平上调以及增强THP-1细胞的吞噬和吞噬能力表现出HSP-S显着的免疫调节特性。 3.总的来说，这项研究表明，HSP-3可以用作功能性食品中的活性成分。

BACKGROUND & AIMS: BACKGROUND:An impairment of the intestinal barrier function is one of the major characteristics of Crohn's disease (CD). This study aimed to evaluate the impact of autophagy induction by rapamycin on the intestinal epithelial barrier function in CD model mice. METHODS:IL-10 knockout (IL-10 KO) mice were used as the human CD models in this study. All the mice were randomly assigned into four groups, (a) wild-type (WT) group; (b) IL-10 KO group; (c) IL-10 KO + rapamycin group and (d) IL-10 KO + 3-methyladenine (3-MA), containing 6 mice in each group. The disease activity index (DAI), histology, pro-inflammatory cytokines and chemotactic factors in colon tissues, intestinal and colonic permeability, distributions and expressions of tight junction (TJ) proteins, epithelial apoptosis of mice in four groups were evaluated and compared. RESULTS:Autophagy induction by rapamycin treatment ameliorated DAI and histological colitis, decreased pro-inflammatory cytokines (TNF-α, IFN-γ and IL-17) and chemotactic factors (CXCL-1 and CXCL-2), decreased intestinal and colonic permeability, improved the distribution and expression of TJ proteins in IL-10 KO mice. CONCLUSION:Autophagy induction by rapamycin significantly improved intestinal barrier function and protected IL-10 KO mice from the experimental chronic colitis.

背景与目标： 背景：肠道屏障功能的损害是克罗恩病（CD）的主要特征之一。这项研究旨在评估雷帕霉素诱导的自噬对CD模型小鼠肠上皮屏障功能的影响。
方法：以IL-10基因敲除小鼠（IL-10 KO）作为人类CD模型。将所有小鼠随机分为四组，（a）野生型（WT）组；（b）野生型（WT）组。 （b）IL-10 KO组； （c）IL-10 KO雷帕霉素组和（d）IL-10 KO 3-甲基腺嘌呤（3-MA），每组6只小鼠。评估并比较了四组小鼠的疾病活动指数（DAI），组织学，结肠组织中的促炎细胞因子和趋化因子，肠和结肠通透性，紧密连接（TJ）蛋白的分布和表达，小鼠上皮细胞凋亡。
结果：雷帕霉素诱导的自噬改善了DAI和组织性结肠炎，降低了促炎细胞因子（TNF-α，IFN-γ和IL-17）和趋化因子（CXCL-1和CXCL-2），降低了肠道和结肠的通透性，改善了IL-10 KO小鼠中TJ蛋白的分布和表达。
结论：雷帕霉素自噬诱导显着改善肠屏障功能，并保护IL-10 KO小鼠免受实验性慢性结肠炎的侵害。