高能震波对缺血性坏死股骨头微血管及组织细胞超微结构的影响

目的 观察高能震波对缺血性坏死股骨头微血管密度(MVD)和组织细胞超微结构的影响,探讨高能震波治疗股骨头缺血性坏死的作用机制. 方法 健康雄性新西兰白兔32只.3.0～4.0kg,平均3.4 kg.联合应用甲泼尼龙和内毒素6周诱发早期股骨头缺血性坏死的动物模型.所有实验兔左后腿作为治疗侧,采用能流密度0.26 mJ/mm2,频率1 Hz,冲击量为2000次的高能震波治疗,右后腿作为对照侧,不予治疗.分别于治疗后4、8、12周对股骨头行微血管墨汁灌注,研究股骨头MVD的变化,制作半薄切片,在透射电镜下分别观察治疗侧和对照侧股骨头组织细胞的超微结构. 结果 高能震波治疗后4～12周,治疗侧股骨头微血管增粗增多,与对照侧相比MVD显著增加(P＜0.05).治疗后8～12周,治疗侧股骨头骨小梁面积百分比显著高于对照侧(P＜0.05).透射电镜下观察可见治疗侧股骨头与对照侧相比成骨细胞和血管内皮细胞数目较多,功能状态活跃. 结论 高能震波治疗能有效促进缺血性坏死股骨头的血管生成,改善成骨细胞和血管内皮细胞的功能状态,加速股骨头坏死的修复.     

支气管哮喘大鼠气道重塑中气道平滑肌细胞凋亡及地塞米松的干预作用

目的 观察支气管哮喘(简称哮喘)大鼠气道重塑中气道平滑肌细胞(airway smoothmuscle cells,ASMC)凋亡及地塞米松对ASMC凋亡的影响.方法 将清洁级雄性SD大鼠按随机数字表法分为正常对照组、哮喘组和地塞米松干预组,每组12只.以卵蛋白致敏和激发的方法制备大鼠慢性哮喘模型.用脱氧核糖核苷酸末端转移酶(TdT酶)介导的dUTP切口末端标记法(TUNEL法)检测ASMC凋亡并计算凋亡指数.用免疫组织化学和原位杂交法分别检测气道平滑肌Bcl-2、Bax蛋白及其mRNA的表达情况.经SPSS 11.5软件进行统计学分析,实验数据用x±s表示.多组间比较采用方差分析,多组样本均数两两比较,两变量的相关程度采用直线相关分析.结果 (1)对照组、哮喘组和干预组大鼠ASMC的凋亡指数分别为:0.201±0.022、0.030±0.016和0.118±0.043;(2)对照组、哮喘组和干预组大鼠气道平滑肌层Bcl-2蛋白表达的吸光度值分别为0.060±0.012、0.112±0.028和0.080±0.010,Bcl-2 mRNA表达的吸光度值分别为0.065±0.019、0.157±0.019和0.099±0.029;(3)对照组、哮喘组和干预组大鼠气道平滑肌层Bax蛋白表达的吸光度值为0.120±0.020、0.062±0.012和0.093±0.010,Bax mRNA表达的吸光度值分别为0.155±0.025、0.074±0.019和0.118±0.031;(4)相关分析结果显示,ASMC的凋亡指数与气道平滑肌厚度以及Bcl-2蛋白的相对含量呈显著负相关(r值分别为-0.860、-0.783,P<0.01);ASMC的凋亡指数与气道平滑肌Bax蛋白相对含量呈正相关(r=0.837,P<0.01).结论 ASMC凋亡的减少可能参与了哮喘气道重塑过程;地塞米松可以增加促凋亡蛋白Box的表达,同时减少抑凋亡蛋白Bcl-2的表达,从而增加ASMC的凋亡.     

糖皮质激素所致骨质疏松症的临床研究进展

糖皮质激素所致骨质疏松症（CIDP）是糖皮质激素（GCs）治疗的严重并发症之一。GCs使骨形成减少,骨吸收增加,在GIOP的发生中起关键作用。短期GCs治疗即可出现骨量丢失及骨折危险性增加,因此早期干预十分重要,治疗措施包括钙剂和维生素D制剂、双膦酸盐、激素替代治疗、选择性雌激素受体调节剂、降钙素、重组人甲状旁腺激素（1—34）和维生素K2等。本文从流行病学、临床特点、诊断、预防和药物干预措施几方面作一综述。     

The role of stress in the mosaic of autoimmunity: An overlooked association

Stress is defined as the pscyophysiological reaction in which the steady state is disturbed or threatened. Stress is not always perceived as a negative response. Stress results when environmental demands exceed an individuals' adaptive capacities. Autoimmune diseases are heterogeneous group of chronic diseases which occur secondary to loss of self antigen tolerance. The etiopathogenesis of autoimmune disease is uncertain. Genetic factors as well as environmental factors appear to interplay, leading to a cascade of events resulting in disease onset. Stress has been postulated to play a role in disease onset in the genetically susceptible patients. During the stress response, catecholamines and glucocorticoids are released from locus coeruleus and adrenal gland. These biomolecules exert control over various immune cells in the innate and adaptive arms of the immune system, thereby altering the cytokine profile released. The increase of IL-4 promotes T-helper 2 (T_h2) cell differentiation, while the decrease in IL-12 and the increased IL-10 production reduce the number of T-helper 1 (T_h1) cells. The relationship between stress and autoimmune diseases is intricate. Stress has been shown to be associated with disease onset, and disease exacerbations in rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, Graves' disease as well as other autoimmune conditions. In certain conditions such as psoriasis, stress has been implicated in delaying lesion clearance upon the application of standard treatment regimes. Finally, psychological therapy and cognitive behavioral therapy aimed to reduce stress levels was shown to be effective in influencing better outcomes in many autoimmune diseases. The purpose of this paper is to closer inspect the clinical evidence regarding the role of stress on influencing the various aspects of disease entities.     

Osteoporosis in children and young adults

Osteoporosis is a major public health problem with serious long-term complications. In children, the definition of osteoporosis is not only based on densitometric criteria but also takes into account vertebral and long bone fragility fractures. Several factors, such as long-term high-dose steroids, chronic inflammation, malnutrition, immobility, lack of sex steroids, and medication can reduce bone density and increase the risk for fragility fractures when left untreated. Also, genetic conditions can predispose to primary bone fragility disorders, with osteogenesis imperfecta being the most common. Furthermore, since the growing skeleton is at an increased rate of bone remodeling, the ability to heal long bone fractures and reshape vertebral fractures differentiates children from adults. The scope of this chapter is to review the risk factors of osteoporosis and fragility fractures and describe the commonest causes of primary and secondary osteoporosis and their management in children and young adults.     

神经免疫性疾病患者糖皮质激素治疗前后白细胞介素2和15变化的临床意义

目的　探讨糖皮质激素 (GC)对神经免疫性疾病 (IND)患者血浆和脑脊液 (CSF)白细胞介素 (IL) 2和IL 15的影响。方法　用双抗体夹心酶联免疫法 (ELISA)检测 2 2例急性期IND患者GC治疗前后血浆和CSFIL 2、IL 15水平 ,与 2 0例脑梗死 (NIND)患者、18例手术 (OP)患者、11例未用GC的重症肌无力患者 (NMG)进行对比。结果　治疗前 4组 (IND ,NIND ,OP和NMG)组间血浆和CSF中IL 2和IL 15比较 ,差异有显著意义 (IL 2 :血浆P <0 0 5 ,CSFP <0 0 1;IL 15 :血浆P <0 0 5 ,CSFP <0 0 5 ) ;治疗前IND组显著高于NIND组和OP组 (P <0 0 1) ,而与NMG组比较 ,差异无显著意义 (P >0 0 5 ) ;GC治疗后IND组IL 2和IL 15低于治疗前 (P <0 0 5 )。结论　急性期IND患者血浆和CSF中的IL 2和IL 15有上升趋势 ,GC治疗后IL 2和IL 15水平降低。GC可能通过影响患者免疫细胞产生IL 2和IL 15 ,而发挥治疗IND的作用。     

长春新碱联合糖皮质激素治疗11例婴儿期Kasabach-Merritt综合征

目的 探讨Kasabach-Merritt（K-M）综合征的有效治疗方案。方法 收集2015—2017年首都医科大学附属北京儿童医院皮肤科收治的11例K-M综合征患儿的临床资料,分析长春新碱联合糖皮质激素治疗的疗效。结果 11例患儿就诊年龄1～212（87.91 ± 72.01） d,男4例、女7例。血管瘤多呈紫红色斑块,质地偏硬,其中5例瘤体周围伴有皮肤紫癜。血小板计数（4 ~ 32） × 109/L。给予口服泼尼松（2 ~ 5） mg·kg-1·d-1与静脉注射长春新碱每周0.05 mg/kg联合治疗。10例患儿应用糖皮质激素联合长春新碱治疗（1.8 ± 1.23）周后血小板达到正常,治疗（3.6 ± 1.26）周后纤维蛋白原恢复正常,治疗（3.9 ± 0.74）周后血管瘤开始软化或缩小。1例治疗5周后,血小板计数仍没有恢复正常,联合使用静脉栓塞后,血小板恢复正常,并可维持。结论 长春新碱联合糖皮质激素治疗可控制K-M综合征患儿瘤体发展,促进血小板恢复。     

siRNA沉默MIF基因对糖皮质激素抑制脂质炎症介质释放的影响及其机制

 目的： 研究小干扰RNA（siRNA）阻断巨噬细胞移动抑制因子（macrophage migration-inhibitory factor,MIF）基因表达对糖皮质激素抑制脂质炎症介质释放的影响及其细胞内机制。方法：体外培养小鼠巨噬细胞系RAW2647,采用免疫荧光法观测siRNA转染效率,RT-PCR检测MIF mRNA的表达,Western blotting检测MIF蛋白的表达;RAW2647细胞转染MIF siRNA后观察地塞米松（Dex）抗炎作用的变化,用ELISA检测细胞上清中前列腺素E2(PGE2)和白三烯B4(LTB4)的含量,Western blotting检测胞浆膜联蛋白Annexin 1和下游胞浆磷酸酯酶A2α（cPLA2α）的蛋白表达变化。结果：与阴性对照相比,MIF siRNA能有效阻断细胞内源性MIF蛋白的表达,增强RAW2647细胞对Dex作用的敏感性;明显增强Dex抑制PGE2和LTB4产生的效应,增加胞浆蛋白Annexin 1的表达,抑制cPLA2α的磷酸化。结论：MIF siRNA能增强糖皮质激素抑制脂质炎症介质PGE2和LTB4的释放,且可能是通过影响Annexin 1-cPLA2α信号通路实现的。阻断内源性MIF蛋白的表达可显著增强RAW2647细胞对糖皮质激素抗炎作用的敏感性。     

早期激素治疗颅底骨折致迟发性面瘫的临床疗效

目的：观察颅底骨折致迟发性面瘫患者早期皮质激素治疗的疗效。方法回顾性分析颅底骨折致迟发性面瘫患者38例,早期（人院后立即给予）激素治疗20例,发现面瘫后给予激素治疗18例。治疗时间均1～2周,其他治疗相同。结果38例患者经保守治疗后均好转恢复,早期激素治疗的患者有效率95.0％（19/20）,恢复时间快;发现面瘫后给予激素治疗的有效率77.8％（14/18）,恢复时间慢。结论颅底骨折致迟发性面瘫患者早期激素治疗,可以明显提高迟发性面瘫患者的临床疗效。     

Involvement of the intrinsic and extrinsic cell‐death pathways in the induction of apoptosis of mature lymphocytes by the Escherichia coli heat‐labile enterotoxin

Escherichia coli heat‐labile enterotoxin (LT) exhibits a broad range of immunomodulatory activities, including the induction of lymphocyte‐programmed cell death. In previous studies, we have demonstrated that in vivo LT promotes apoptosis of immature T and B cells through the stimulation of endogenous glucocorticoids. In the present study, we show that the extrinsic cell‐death pathway as well as the apoptosis‐inducing factor do not participate in the LT‐induced elimination of thymocytes. In contrast to developing lymphocytes, LT promotes the death of mature lymphocytes by both glucocorticoid‐ and Fas death receptor/Fas ligand‐dependent mechanisms. However, the dependency of these mechanisms in the LT‐induced cell‐death activity seems to be different among CD4⁺ and CD8⁺ T cells. Altogether, our study shows that the same bacterial toxin can induce apoptosis of lymphoid cells through several mechanisms depending on the status of differentiation of these cells.