防己茯苓汤对急性肾损伤患者肾组织蛋白表达的影响

目的:观察防己茯苓汤对急性肾损伤患者肾组织蛋白表达的影响。方法:将150例急性肾损伤患者随机分为治疗组和对照组,每组75例,对照组患者均予基础治疗,包括:饮食控制、营养支持,血压及血糖管理,维持水、电解质及酸碱平衡,祛除诱因、对原发病给予治疗,停用可疑致肾损伤药物。治疗组在对照组治疗基础上加服防己茯苓汤治疗,方药组成:防己9 g,黄芪9 g,茯苓18 g,桂枝9 g,甘草6 g,每日1剂。治疗28 d后采集血液及尿液标本检测血利钠肽(natriuretic peptide,ANP)和尿β2-微球蛋白,用生化仪测定血肌酐(serum creatinine,Scr)、血清半胱氨酸蛋白酶抑制剂C(serum cystatin C,Cys C)的变化。结果:两组患者ANP、尿β2-微球蛋白、Cys C比较,差异均有统计学意义(P0.05);两组患者Scr比较,差异无统计学意义(P0.05)。结论:防己茯苓汤对急性肾损伤疗效显著,且能改善患者临床检验指标。     

White matter hyperintensities mediate the impact of amyloid ß on future freezing of gait in Parkinson's disease

BackgroundFreezing of gait (FOG) is a common symptom in Parkinson's Disease (PD) patients. Previous studies have reported relationships between FOG, substantia nigra (SN) degeneration, dopamine transporter (DAT) concentration, as well as amyloid β deposition. However, there is a paucity of research on the concurrent impact of white matter damage.ObjectivesTo assess the inter-relationships between these different co-morbidities, their impact on future FOG and whether they act independently of each other.MethodsWe used baseline MRI and longitudinal gait data from 423 de novo PD patients from the Parkinson's Progression Markers Initiative (PPMI). We used deformation based morphometry (DBM) from T1-weighted MRI to measure SN atrophy, and segmentation of white matter hyperintensities (WMH) as a measure of WM pathological load. Putamen and caudate DAT levels from SPECT as well as cerebrospinal fluid (CSF) amyloid β were obtained directly from the PPMI. Following correlation analyses, we investigated whether WMH burden mediates the impact of amyloid β on future FOG.ResultsSN DBM, WMH load, putamen and caudate DAT activity and CSF amyloid β levels were significantly different between PD patients with and without future FOG (p < 0.008). Mediation analysis demonstrated an effect of CSF amyloid β levels on future FOG via WMH load, independent of SN atrophy and striatal DAT activity levels.ConclusionsAmyloid β might impact future FOG in PD patients through an increase in WMH burden, in a pathway independent of Lewy body pathology.     

Profilin 1 knockdown prevents ischemic brain damage by promoting M2 microglial polarization associated with the RhoA/ROCK pathway

Microglial polarization to the anti-inflammatory M2 phenotype is essential in resolving neuroinflammation, making it a promising therapeutic strategy for stroke intervention. The actin cytoskeleton is known to be important for the physiological functions of microglia, including migration and phagocytosis. Profilin 1 (PFN1), an actin-binding protein, is involved in the dynamic transformation and reorganization of actin. However, the role of PFN1 in microglial polarization and ischemia/reperfusion injury is unclear. The role of PFN1 on microglial polarization was examined in vitro in BV2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGDR) and in vivo in male mice after transient middle cerebral artery occlusion (MCAO). Knockdown of PFN1 inhibited M1 microglial polarization and promoted M2 microglia polarization 48 hr after OGDR stimulation in BV2 cells and 7 days after MCAO-induced injury in male mice. RhoA/ROCK pathway was involved in the regulation of PFN1 during microglial polarization. Knockdown of PFN1 also significantly attenuated brain infarcts and edema, improved cerebral blood flow and neurological deficits in MCAO-injured mice. Inhibition of PFN1 effectively protected the brain against ischemia/reperfusion injuries by promoting M2 microglial polarization in vitro and in vivo.     

Apolipoprotein E ε4 genotype and risk of freezing of gait in Parkinson's disease

ObjectiveTo investigate the association between Apolipoprotein E (APOE) genotype and freezing of gait (FOG) in Parkinson's disease (PD).MethodsThis cohort study included 339 early PD patients who were divided into APOE ε4-positive (n = 88) and ε4-negative (n = 251) groups. They were followed-up for up to 6 years to identify the development of FOG. To investigate the influence of CSF β-amyloid 1–42 (Aβ₄₂) on the association between APOE ε4 and FOG, the patients were additionally dichotomized into “high-level” and “low-level” groups using three different cutoff values for the CSF Aβ₄₂ levels.ResultsAt baseline, the APOE ε4-positive group had lower CSF Aβ₄₂ levels than the APOE ε4-negative group. During a median follow-up of 5.0 years, the APOE ε4-positive group had a higher incidence of FOG than the APOE ε4-negative group. In the multivariable Cox model excluding CSF Aβ₄₂, APOE ε4 was a significant predictor of FOG. However, after adding CSF Aβ₄₂ in the model, APOE ε4 did not survive, whereas lower CSF Aβ₄₂ levels were associated with FOG. In the subgroup analyses, the effect of the APOE ε4 allele was not found in the “low-level” group. However, in the “high-level” group, the APOE ε4 allele independently increased the risk of FOG, and this association was stronger than the association with CSF Aβ₄₂.ConclusionThe APOE ε4 allele may be a novel genetic risk factor for FOG in PD. This association seemed to be mainly mediated by Aβ-dependent pathways, but its Aβ-independent effects might also contribute to the development of FOG.     

Leishmania infantum infection reduces the amyloid β42-stimulated NLRP3 inflammasome activation

Activation of the NLRP3 inflammasome has been shown to play a major role in the neuroinflammation that accompanies Alzheimer’s disease (AD); interventions that down regulate the NLRP3 inflammasome could thus be beneficial in AD. Parasite infections were recently shown to be associated with improved cognitive functions in Apolipoprotein E4 (ApoE4)-expressing members of an Amazonian tribe. We verified in an in vitro model whether Leishmania infantum infection could reduce NLRP3. Results obtained in an initial experimental model in which PBMC were LPS primed and nigericin-stimulated showed that L. infantum infection significantly reduced ASC-speck formation (i.e. intracellular inflammasome proteins assembly), as well as the production of activated caspase 5 and IL-1β, but increased that of activated caspase 1 and IL-18. Moreover, L. infantum infection induced the generation of an anti-inflammatory milieu by suppressing the production of TNFα and increasing that of IL-10. These results were replicated when cells that had been LPS-primed were stimulated with Aβ₄₂ and infected with L. infantum. Results herein indicate that Leishmania infection favors an anti-inflammatory milieu, which includes the down-regulation of NLRP3 inflammasome activation, possibly to facilitate its survival inside host cells. A side effect of Leishmaniasis would be the hampering of neuroinflammation; this could play a protective role against AD development.     

新诊断2型糖尿病患者骨钙素与胰岛素抵抗、胰岛β细胞功能及血脂的相关性研究

目的探讨新诊断2型糖尿病(T2DM)患者血清骨钙素(OC)与胰岛素抵抗、胰岛β细胞功能及血脂的关系。方法本研究为病例对照研究,病例组为2016年1月至2017年7月间我院内分泌科新诊断的2型糖尿病患者(符合WHO 1999年糖尿病诊断标准)150人,对照组来源于同期于我院进行健康体检的人群,共50人。比较两组的OC水平,并分析T2DM患者OC与空腹血糖(FBG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)和高密度脂蛋白(HDL)等指标的相关性。结果病例组OC低于对照组[(16.85±5.60)ng/ml vs(24.63±6.93)ng/ml],HOMA-IR高于对照组(10.88±8.71 vs 1.33±0.95),HOMA-β低于对照组(28.42±17.72 vs 134.65±67.73),TG高于对照组[(4.28±2.38)ng/ml vs(1.37±0.38)mmol/L],HDL低于对照组[(0.76±0.18)ng/ml vs(1.11±0.26)mmol/L],P均<0.001;新诊断T2DM患者OC与FBG、HbA1c呈负相关,与空腹C肽(FCP)呈正相关,相关系数分别为-0.315、-0.321、0.434(P<0.05)。结论新诊断T2DM患者的血清骨钙素低于健康人群,其对2型糖尿病的发生及监测有一定临床意义。     

107株阴沟肠杆菌产ESBLs和AmpC酶检测及耐药性分析

目的 了解近年来临床分离的阴沟肠杆菌对常用抗菌药物的敏感性,并检测分离株产超广谱β-内酰胺酶(ESBLs)和AmpC酶的情况,指导临床合理用药。 方法 收集2016年1-12月湖南中医药大学第一附属医院分离自临床标本的阴沟肠杆菌,采用Vitek-2 Compact进行常规药敏试验,采用表型确证试验检测ESBLs,采用三维试验检测AmpC酶。 结果 共收集非重复分离阴沟肠杆菌107株,主要来源于呼吸内科(26/107,24.3%)、骨伤科(21/107,19.6%)、中心ICU(20/107,18.7%)等科室,以痰液(38/107,35.5%)和伤口分泌物(29/107,27.1%)等标本为主;阴沟肠杆菌对青霉素类、三代头孢菌素和头霉素类高度耐药,对哌拉西林/他唑巴坦、头孢吡肟、亚胺培南耐药率分别为13.1%、22.4%、0.9%。共检测出单产ESBLs菌株30株(28.0%),单产AmpC酶的菌株35株(32.7%);同时产ESBLs和AmpC酶菌株14株(13.1%);同时产ESBLs和AmpC酶菌株对常用抗菌药物的耐药率高于不产酶株,差异均有统计学意义(均P＜0.05)。 结论 产ESBLs、AmpC酶是阴沟肠杆菌多重耐药的重要机制;阴沟肠杆菌产酶株的检测,对指导临床抗菌治疗具有重要意义。