Preexisting antigen‐specific immune responses are modulated by oral KLH feeding in humans

Oral tolerance is the antigen‐specific inhibition of a systemic immune response after oral antigen uptake and well established in animal models. We recently showed that keyhole limpet hemocyanin (KLH) feeding modulates subsequently induced systemic immune responses in humans as well. In the present study, we investigated whether oral KLH can also modulate preexisting antigen‐specific systemic B‐ and T‐cell responses. We induced delayed‐type hypersensitivity (DTH) reactions as well as systemic KLH‐specific B‐ and T‐cell responses by subcutaneous KLH injections. Subsequent oral KLH administration decreased the small proportion of antigen‐specific CD4⁺ T cells positive for the cytokine IL‐17 at the end of the feeding regimen even further. After reimmunization, there was no difference in DTH reactions and the KLH‐specific B‐cell responses, but KLH‐fed volunteers had an increased proportion of antigen‐specific CD4⁺ T cells positive for IL‐10 and a reduced proportion of antigen‐specific CD4⁺ T cells positive for the skin‐homing receptor cutaneous lymphocyte antigen and IL‐2 and IFN‐γ. Taken together, oral KLH can modulate a preexisting systemic KLH‐specific immune response. These results suggest that feeding antigen may offer therapeutic strategies for the suppression of unwanted immune reactions in humans.     

Chronic obstructive pulmonary disease and asthma-associated Proteobacteria,but not commensal Prevotella spp., promote Toll-like receptor 2-independent lung inflammation and pathology

Recent studies of healthy human airways have revealed colonization by a distinct commensal bacterial microbiota containing Gram-negative Prevotella spp. However, the immunological properties of these bacteria in the respiratory system remain unknown. Here we compare the innate respiratory immune response to three Gram-negative commensal Prevotella strains (Prevotella melaninogenica, Prevotella nanceiensis and Prevotella salivae) and three Gram-negative pathogenic Proteobacteria known to colonize lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma (Haemophilus influenzae B, non-typeable Haemophilus influenzae and Moraxella catarrhalis). The commensal Prevotella spp. and pathogenic Proteobacteria were found to exhibit intrinsic differences in innate inflammatory capacities on murine lung cells in vitro. In vivo in mice, non-typeable H. influenzae induced severe Toll-like receptor 2 (TLR2)-independent COPD-like inflammation characterized by predominant airway neutrophilia, expression of a neutrophilic cytokine/chemokine profile in lung tissue, and lung immunopathology. In comparison, P. nanceiensis induced a diminished neutrophilic airway inflammation and no detectable lung pathology. Interestingly, the inflammatory airway response to the Gram-negative bacteria P. nanceiensis was completely TLR2-dependent. These findings demonstrate weak inflammatory properties of Gram-negative airway commensal Prevotella spp. that may make colonization by these bacteria tolerable by the respiratory immune system.     

丙种球蛋白联合甲泼尼松龙治疗小儿吉兰－巴雷综合征呼吸肌麻痹的临床研究

目的：研究丙种球蛋白联合甲泼尼松龙治疗小儿吉兰－巴雷综合征（GBS ）呼吸肌麻痹的临床疗效,企为临床治疗此病提供更有效的方法。方法：从在我院进行治疗的小儿GBS呼吸肌麻痹患者中,选取64例患者,并签订知情协议书。按照是否具有使用丙种球蛋白治疗的经济能力将患者分为实验组和对照组。实验组使用丙种球蛋白联合甲泼尼松龙治疗,对照组单纯使用甲泼尼松龙治疗,分别观察两组患者的休斯（H ug hes ）评分、疗效和不良反应。结果：试验组患者治疗的有效率为94％,显著高于对照组的69％（ P＝0．010）;在患者接受治疗后15 d ,试验组患者的 H ug hes评分是（2．69±1．23）分,明显低于对照组患者（3．34±0．85）分（P＝0．017）,且在患者接受治疗后6个月时,实验组患者的H ug hes评分是（1．29±0．94）分,亦明显低于对照组患者的（1．87±0．76）分（ P＝0．028）;实验组不良反应的发生率为16％,而对照组不良反应的发生率为22％（ P＝0．522）,差异不具有统计学意义。结论：与单纯使用甲泼尼松龙治疗小儿GBS呼吸肌麻痹相比,使用丙种球蛋白联合甲泼尼松龙治疗的疗效更为显著,且安全性较高,有利于患者病情的早期康复。     

环磷酰胺联合人免疫球蛋白治疗系统性红斑狼疮的疗效及其对患者血清MCP-4和IL-4的影响

目的探讨环磷酰胺联合人免疫球蛋白治疗系统性红斑狼疮的疗效及其对患者血清单核细胞趋化蛋白-4(MCP-4)和白细胞介素-4(IL-4)的影响。方法选取2010年5月至2014年5月我院收治的72例系统性红斑狼疮患者为研究对象,随机将其分为对照组和观察组,每组36例。对照组给予环磷酰胺+强的松治疗,观察组给予人免疫球蛋白+环磷酰胺+强的松治疗。治疗4周后评价两组患者的疗效,并比较两组患者系统性红斑狼疮疾病活动指数(SLEDAI)积分及24 h尿蛋白水平。结果治疗后观察组患者的总有效率为91.7%,高于对照组的72.2%,差异具有统计学意义(P<0.05)。治疗后,观察组患者的血清MCP-4(137.30±13.27)pg/ml、IL-4(3.44±0.53)pg/ml都低于对照组患者的血清MCP-4(168.26±14.12)pg/ml、IL-4(5.04±0.48)pg/ml,差异均具有统计学意义(P<0.05)。治疗后,观察组患者的SLEDAI评分(8.22±2.27)分、24 h尿蛋白(1.31±1.03)g都低于对照组患者的SLEDAI评分(10.14±3.18)分、24 h尿蛋白(2.78±2.39)g,差异均具有统计学意义(P<0.05)。两组不良反应比较差异无统计学意义(P>0.05)。结论环磷酰胺联合人免疫球蛋白治疗系统性红斑狼疮疗效显著,能够有效降低血清IL-4及MCP-4水平,同时能够有效恢复Th1和Th2细胞免疫平衡。     

血清HE4、TSGF和CA125联合检测诊断卵巢癌的价值

目的：探讨血清人附睾蛋白4(HE4)、肿瘤特异性生长因子(TSGF)和肿瘤抗原(CA125)联合检测对卵巢癌的诊断价值。方法选取卵巢癌患者70例为研究对象,另选择60例卵巢良性肿瘤患者为对照组,检测并比较卵巢良性肿瘤、卵巢癌Ⅰ期及卵巢癌Ⅱ、Ⅲ期间HE4、CA125及TSGF水平的差异。观察HE4、CA125及TSGF与卵巢癌侵袭性关系(周围浸润、淋巴结转移及复发),并分析单项指标及联合应用对卵巢癌诊断的敏感性、特异性、阳性预测值、阴性预测值及诊断效率。结果卵巢良性肿瘤、卵巢癌Ⅰ期及卵巢癌Ⅱ、Ⅲ期三组比较, HE4、CA125及TSGF呈递增趋势,且三组间比较差异具有统计学意义(P<0.05)。与不伴有周围浸润、淋巴结转移及复发的卵巢癌比较,存在周围浸润、淋巴结转移及复发的卵巢癌患者HE4、CA125及TSGF水平均显著升高,差异具有统计学意义(P<0.05)。单项比较,CA125诊断敏感性最高,HE4诊断特异性及诊断效率最高。与单项指标比较,联合检测的敏感性、阳性预测值、阴性预测值及诊断效率更高,且差异具有统计学意义(P<0.05)。结论血清HE4、TSGF和CA125联合检测对卵巢癌诊断效率高,值得临床推广应用。     

海南地区人乳头瘤病毒感染情况与亚型分析

目的：了解常见21种人乳头瘤病毒(HPV)在海南地区的亚型分布、多重感染和不同年龄感染情况。方法使用PCR体外扩增和膜杂交法对2013年1~12月来我院就诊的10764例女性进行HPV分型检查。结果10764例样本中阳性率为19.38%,多重感染率为4.96%,25岁以下阳性率最高,各亚型检出率最高依次为52型、16型和58型,未检出43型。结论海南地区主要HPV感染亚型为52型、16型和58型,HPV感染有低龄化趋势。     

Production of reflex cough by brainstem respiratory networks

Delineation of neural mechanisms involved in reflex cough is essential for understanding its many physiological and clinical complexities, and the development of more desirable antitussive agents. Brainstem networks that generate and modulate the breathing pattern are also involved in producing the motor patterns during reflex cough. Neurones of the ventrolateral medulla respiratory pattern generator mutually interact with neural networks in the pons, medulla and cerebellum to form a larger dynamic network. This paper discusses evidence from our laboratory and others supporting the involvement of the nucleus tractus solitarii, midline raphe nuclei and lateral tegmental field in the medulla, and the pontine respiratory group and cerebellum in the production of reflex cough. Gaps in our knowledge are identified to stimulate further research on this complicated issue.