生长因子Progranulin的结合受体和生物学功能

生长因子颗粒素蛋白前体（progranulin, PGRN）广泛存在于动物和植物组织中.研究证明,哺乳动物的PGRN是一个多功能分子,在组织/器官发育、细胞分化、肿瘤发生发展、炎症应答以及神经退行性疾病中均具有重要的作用.PGRN发挥生物学功能需要和多种结合蛋白相互结合,例如sortilin、Toll样受体9（TLR9）、肿瘤坏死因子受体（TNFR）及分泌性淋巴细胞蛋白酶抑制因子（SLPI）等. 本文将对PGRN的结合受体和生物学功能进行综述.     

Localization of endothelin receptors in bleomycin-induced pulmonary fibrosis in the rat

Pulmonary fibrosis is characterized by excessive extracellular matrix deposition with concomitant loss of gas exchange units, and endothelin-1 (ET-1) has been implicated in its pathogenesis. Increased levels of ET-1 from tissues and bronchoalveolar lavage have been reported in patients with pulmonary fibrosis and in animal models after intratracheal bleomycin. We characterized the cellular distribution of alveolar ET receptors by immunohistochemistry in bleomycin-induced pulmonary fibrosis in the rat and determined the regulation by bleomycin of ET receptor mRNA expression in isolated alveolar macrophages and rat lung fibroblasts. We found significant increases in the numbers of fibroblasts and macrophages at day 7 compared to day 28 and control animals. ET_B receptor immunoreactivity was observed on fibroblasts and invading monocytes. Isolated fibroblasts expressed both ET_A and ET_B receptor mRNA, and ET_A receptor mRNA was upregulated by bleomycin. Isolated resident alveolar macrophages expressed neither ET_A nor ET_B receptor mRNA which were also not induced by bleomycin. We conclude that, while ET_B receptor stimulation of fibroblasts and monocytes recruited during bleomycin-induced lung injury exerts antagonistic effects on fibroblast collagen synthesis, the observed increase in the number of fibroblasts in vivo and upregulation of fibroblast ET_A receptor mRNA by bleomycin in vitro point to a predominance of the profibrotic effects of ET receptor engagement.     

Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis

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自发性高血压大鼠多组织炎症状态

高血压是一种慢性血管性疾病,易累及肾、肝、心、脑等组织,引起脑卒中和心、肾损害等并发症.本研究对高血压时肾、肝、心、脑等组织的炎症状态进行了观察.实验采用自发性高血压大鼠(spontaneously hypertensive rat,SHR)和正常血压的Wistar-Kyoto(WKY)大鼠,用RT-PCR和Western blot法观察肾、肝、心、脑等组织炎症相关因子IL-1p、TNFα、ICAM-1、iNOS、C/EBPδ和PPARγ的基因表达;紫外分光光度法观察蛋白质羰基化水平和FRAP法检测组织总抗氧化能力.结果显示(1)SHR组织炎症相关因子表达较对照WKY增强,除IL-1βmRNA在肝和脑的增加不明显外,其余均有显著性差异(P＜0.05);(2)SHR和WKY大鼠肾、心、脑蛋白质羰基化水平(nmol/mg蛋白)分别为8.93±1.08和2.27±0.43、2.23±0.23和0.17±0.02、13.42±1.10和5.72±1.01,SHR明显增加(P＜0.05);而肝脏蛋白质羰基化水平无明显变化;(3)SHR肾、肝、心、脑总抗氧化能力水平显著低于WKY大鼠(P＜0.05).以上结果表明,SHR多个组织(肾、肝、心和脑)均存在炎症因子被诱导和氧化应激反应等明显的炎症状态,提示炎症可能在高血压及其并发症的病理改变中起重要作用.     

Complement activation,regulation, and molecular basis for complement‐related diseases

The complement system is an essential element of the innate immune response that becomes activated upon recognition of molecular patterns associated with microorganisms, abnormal host cells, and modified molecules in the extracellular environment. The resulting proteolytic cascade tags the complement activator for elimination and elicits a pro‐inflammatory response leading to recruitment and activation of immune cells from both the innate and adaptive branches of the immune system. Through these activities, complement functions in the first line of defense against pathogens but also contributes significantly to the maintenance of homeostasis and prevention of autoimmunity. Activation of complement and the subsequent biological responses occur primarily in the extracellular environment. However, recent studies have demonstrated autocrine signaling by complement activation in intracellular vesicles, while the presence of a cytoplasmic receptor serves to detect complement‐opsonized intracellular pathogens. Furthermore, breakthroughs in both functional and structural studies now make it possible to describe many of the intricate molecular mechanisms underlying complement activation and the subsequent downstream events, as well as its cross talk with, for example, signaling pathways, the coagulation system, and adaptive immunity. We present an integrated and updated view of complement based on structural and functional data and describe the new roles attributed to complement. Finally, we discuss how the structural and mechanistic understanding of the complement system rationalizes the genetic defects conferring uncontrolled activation or other undesirable effects of complement.     

Protective action of the peroxisome proliferator-activated receptor-gamma agonist pioglitazone in a mouse model of Parkinson's disease

We examined the effect of pioglitazone, a peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist of the thiazolidinedione class, on dopaminergic nerve cell death and glial activation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. The acute intoxication of C57BL/6 mice with MPTP led to nigrostriatal injury, as determined by tyrosine hydroxylase (TH) immunocytochemistry, and HPLC detection of striatal dopamine and metabolites. Damage to the nigrostriatal dopamine system was accompanied by a transient activation of microglia, as determined by macrophage antigen-1 (Mac-1) and inducible nitric oxide synthase (iNOS) immunoreactivity, and a prolonged astrocytic response. Orally administered pioglitazone (approximately 20 mg/kg/day) attenuated the MPTP-induced glial activation and prevented the dopaminergic cell loss in the substantia nigra pars compacta (SNpc). In contrast, there was little reduction of MPTP-induced dopamine depletion, with no detectable effect on loss of TH immunoreactivity and glial response in the striatum of pioglitazone-treated animals. Low levels of PPARgamma expression were detected in the ventral mesencephalon and striatum, and were unaffected by MPTP or pioglitazone treatment. Since pioglitazone affects primarily the SNpc in our model, different PPARgamma-independent mechanisms may regulate glial activation in the dopaminergic terminals compared with the dopaminergic cell bodies after acute MPTP intoxication.     

急性加重期慢性阻塞性肺疾病患者痰色评分与肺部微生物和病情严重程度的相关性CSCD

目的 探讨急性加重期慢性阻塞性肺疾病患者痰色评分与肺部微生物、病情严重程度的相关性。方法 选择2018年3月至2019年9月我院收治的122例急性加重期慢性阻塞性肺疾病患者,根据其痰色评分分为1~2分组(n=30)与3~4分组(n=92),比较两组患者肺部微生物分布、病情严重程度分布、慢性阻塞性肺疾病评估测试(CAT)评分、白细胞(WBC)水平、C反应蛋白(CRP)水平,分析急性加重期慢性阻塞性肺疾病患者痰色评分与肺部微生物、病情严重程度的相关性。结果 3~4分组患者肺部肺炎克雷伯菌、铜绿假单胞菌、金黄色葡萄球菌、肺炎链球菌、草绿色链球菌、白假丝酵母、酵母样真菌、丝状真菌检出率与1~2分组比较差异无统计学意义(均P>0.05)。3~4分组患者鲍曼不动杆菌检出率显著高于1~2分组(P<0.05)。3~4分组患者病情严重程度分布与1~2分组比较差异有统计学意义(P<0.05)。3~4分组患者CAT评分、WBC水平、CRP水平均显著高于1~2分组(均P<0.05)。急性加重期慢性阻塞性肺疾病患者痰色评分与肺炎克雷伯菌、铜绿假单胞菌、金黄色葡萄球菌、肺炎链球菌、草绿色链球菌、白假丝酵母、酵母样真菌、丝状真菌检出率无显著相关性(均P>0.05),而与鲍曼不动杆菌检出率、CAT评分、WBC水平、CRP水平、病情严重程度呈显著相关性(均P<0.05)。结论 痰色评分与急性加重期慢性阻塞性肺疾病患者肺部微生物和病情严重程度关系密切,有望成为临床评价该类患者肺部微生物分布及病情严重程度的方法之一。     

慢性阻塞性肺疾病稳定期患者血清VAP-1、MSP、SDF-1水平与肺功能、炎性因子及生活质量的关系研究

摘要 目的：探讨慢性阻塞性肺疾病（COPD）稳定期患者血清血管黏附蛋白-1（VAP-1）、巨噬细胞刺激蛋白（MSP）、基质细胞衍生因子-1（SDF-1）水平与肺功能、炎性因子及生活质量的关系。方法：选取我院2018年9月～2020年9月收治的COPD稳定期患者116例作为COPD组,选取同期于我院体检的健康志愿者100例作为对照组。比较两组血清VAP-1、MSP、SDF-1水平以及肺功能指标[第1秒用力呼气容积（FEV1）、用力肺活量（FVC）、FEV1/FVC、最大呼气流速（PEF）]、炎症因子[白介素-6（IL-6）、白介素-17（IL-17）、白介素-22（IL-22）、肿瘤坏死因子-α（TNF-α）]水平。根据COPD稳定期患者的严重程度,分成轻度组（n=53）、中度组（n=34）、重度组（n=29）,比较三组上述各指标水平。采用COPD评估测试表（CAT）评估三组生活质量并进行比较,经Pearson线性相关分析血清VAP-1、MSP、SDF-1水平与肺功能、炎性因子及CAT评分的相关性。结果：COPD组血清VAP-1、MSP、SDF-1、IL-6、IL-17、IL-22及TNF-α水平均高于对照组,而FEV1、FVC、FEV1/FVC以及PEF低于对照组（P＜0.05）。轻度组血清VAP-1、MSP、SDF-1、IL-6、IL-17、IL-22、TNF-α水平及CAT评分较中度、重度组明显降低,且中度组低于重度组,而轻度组FEV1、FVC、FEV1/FVC、PEF较中度、重度组增高,且中度组高于重度组（P＜0.05）。Pearson线性相关分析提示,血清VAP-1、MSP、SDF-1水平与FEV1、FVC、FEV1/FVC、PEF呈负相关,三者与血清IL-6、IL-17、IL-22、TNF-α水平及CAT评分呈正相关（P＜0.05）。结论：COPD稳定期患者的血清VAP-1、MSP、SDF-1水平明显上调,且三者与患者的肺功能、炎症因子及生活质量密切相关,临床有望通过测定血清VAP-1、MSP、SDF-1水平,评估COPD稳定期患者病情进展情况。     

急性血源性骨髓炎全身与局部抗生素治疗体会及重症病例分析

目的:总结急性血源性骨髓炎尤其是重症患者治疗中全身及局部抗生素应用的经验、方法及临床疗效。方法:回顾性分析空军军医大学第二附属医院2016年11月至2019年4月收治的12例急性血源性骨髓炎患者,其中3例为合并肺脓肿的重症败血症患者。对患者首先进行经验性全身抗生素治疗,并进行细菌学分析,然后根据药敏结果进行系统抗生素调整,采用万古霉素负载的硫酸钙/磷酸钙复合物进行局部抗生素缓释治疗,分析治疗前后实验室指标变化、局部影像学变化。结果:细菌学培养显示金黄色葡萄球菌10例,人葡萄球菌1例,阴沟肠杆菌1例;平均随访56.6周;治疗后患者白细胞(WBC)、中性粒细胞百分比(NEUT%)、红细胞沉降率(ESR)、高敏C反应蛋白(hs-CRP)等指标均恢复到正常范围内;影像学显示患者病灶处骨重建及新骨形成良好,无感染复发迹象;12例患者中成功治愈11例,治愈率91.7%;1例转为慢性骨髓炎,二期手术后痊愈;其中3例骨髓炎合并重症败血症、肺脓肿患者经系统抗生素及外科治疗,全部治愈。结论:急性血源性骨髓炎的致病菌主要为甲氧西林敏感金黄色葡萄球菌(MSSA),其治疗要在早诊断的前提下,率先经验性应用抗生素,然后根据药敏结果合理选择足量敏感抗生素。苯唑西林在3例合并败血症、肺脓肿的重症患者治疗中起到了关键作用,同时局部采用硫磷复合物负载万古霉素进行治疗,既可以实现局部抗感染作用,又可以促进新骨形成,有效控制全身感染、消除败血症,临床疗效满意。     

双水平气道正压通气治疗重叠综合征合并呼吸衰竭患者的临床疗效

目的：探讨鼻面罩双水平正压通气（BIPAP）治疗重叠综合征合并呼吸衰竭患者的临床疗效及对血气指标和肺功能的影响。 方法：选取2011 年10 月到2014 年6 月期间我院收治的重叠综合征合并呼吸衰竭患者46 例,将其随机分为观察组（23 例）和对 照组（23 例）,在常规抗感染、支气管扩张剂、激素、纠正酸碱失衡、呼吸兴奋剂、针对原发病等治疗基础上,对照组给予持续气道正 压通气(CPAP),观察组给予BIPAP 通气治疗,对比治疗后两组患者的临床疗效,比较两组治疗前后24h 动脉血气、肺功能以及多 导睡眠监测(PSG)结果。结果：治疗后,观察组患者的总有效率为87.0%（20/23）,显著高于对照组的73.9%(17/23),差异有统计学意 义（P<0.05）;两组患者的24 h动脉血气、肺功能和PSG 结果均显著优于治疗前,且观察组优于对照组,差异具有统计学意义（P<0. 05）。结论：BIPAP治疗重叠综合征合并呼吸衰竭临床疗效显著,可以改善患者的血气指标及肺功能,有效降低气管插管率,值得 在临床推广应用。