噻托溴铵粉雾剂联合沙美特罗替卡松粉吸入剂治疗慢性阻塞性肺疾病急性加重期伴呼吸衰竭的临床研究

目的观察噻托溴铵粉雾剂联合沙美特罗替卡松粉吸入剂治疗慢性阻塞性肺疾病(COPD)急性加重期伴呼吸衰竭的临床疗效及安全性。方法将76例COPD急性加重期伴呼吸衰竭患者随机分为对照组38例和试验组38例。对照组予以常规治疗配合呼吸机辅助通气治疗;试验组在对照组治疗的基础上,予以沙美特罗替卡松粉吸入剂每次1吸,bid,吸入治疗+噻托溴铵粉雾剂每次18μg,qd,吸入治疗。2组患者均治疗2周。比较2组患者的临床疗效、动脉血气指标、降钙素原和免疫功能,以及药物不良反应的发生情况。结果治疗后,试验组和对照组的总有效率分别为92.11%(35例/38例)和73.68%(28例/38例),差异有统计学意义(P<0.05)。治疗后,试验组和对照组的动脉血氧分压分别为(86.35±7.04)和(77.49±6.85)mm Hg,氧合指数分别为(310.89±29.87)和(281.34±27.53)mm Hg,降钙素原分别为(1.42±0.54)和(1.93±0.61)ng·m L^-1,肿瘤坏死因子-α分别为(275.49±48.62)和(310.05±54.73)ng·L^-1,白细胞介素-8分别为(312.62±75.64)和(389.75±78.76)pg·m L^-1,超敏C-反应蛋白分别为(4.73±2.45)和(8.34±2.53)mg·L^-1,差异均有统计学意义(均P<0.05)。2组患者治疗期间均未发生药物不良反应。结论噻托溴铵粉雾剂联合沙美特罗替卡松粉吸入剂治疗COPD急性加重期伴呼吸衰竭的临床疗效确切,其能显著降低患者的降钙素原水平,改善患者的血气指标和免疫功能,且安全性较好。     

Neuroprotective effect of gold nanoparticles composites in Parkinson's disease model

Parkinson’s disease (PD) is second most common neurodegenerative disorder worldwide. Although drugs and surgery can relieve the symptoms of PD, these therapies are incapable of fundamentally treating the disease. For PD patients, over-expression of α-synuclein (SNCA) leads to the death of dopaminergic neurons. This process can be prevented by suppressing SNCA over-expression through RNA interference. Here, we successfully synthesized gold nanoparticles (GNP) composites (CTS@GNP-pDNA-NGF) via the combination of electrostatic adsorption and photochemical immobilization, which could load plasmid DNA (pDNA) and target specific cell types. GNP was transfected into cells via endocytosis to inhibiting the apoptosis of PC12 cells and dopaminergic neurons. Simultaneously, GNP composites are also used in PD models in vivo, and it can successfully cross the blood-brain barrier by contents of GNP in the mice brain. In general, all the works demonstrated that GNP composites have good therapeutic effects for PD models in vitro and in vivo.     

倍氯米松软膏与维A酸乳膏治疗皮肤丘疹型淀粉样变的临床疗效比较

目的 比较倍氯米松软膏与维A酸乳膏治疗皮肤丘疹型淀粉样变的临床疗效.方法 将皮肤丘疹型淀粉样变100例患者按随机数字表法分为观察组和对照组,每组各50例,对照组采用维A酸乳膏治疗,观察组上采用倍氯米松软膏治疗,治疗4周后,比较两组患者皮损面积、浸润情况、皮肤颜色、皮肤瘙痒评分,以及痊愈率和有效率.结果 （1）两组患者治疗后,症状好转,症状评分较治疗前逐渐减低,观察组于第1周、第2周、第3周、第4周评分分别为（9.35±1.88）分、（6.54 ±2.16）分、（4.08±1.32）分、（2.04±0.95）分,明显优于对照组的（10.86±2.08）分、（7.98 ±2.57）分、（6.25±1.44）分、（4.56±1.18）分,比较差异具有统计学意义（t =6.22、6.71、7.30、7.41,均P＜0.05）;（2）两组患者治疗4周后,观察组有效率和治愈率分别为94％和34％明显高于对照组的70％和22％,两组比较差异具有统计学意义（x2=9.040、8.391,均P＜0.05）.结论 倍氯米松软膏在治疗皮肤丘疹型淀粉样变方面较维A酸乳膏症状改善明显,临床效果确切,值得积极推广应用.     

Validation of an HPLC Analytical Method for the Quantitative/Qualitative Determination of Fluticasone Propionate in Inhalation Particles on Several Matrices

Fluticasone propionate is a highly potent corticosteroid used to treat asthma and allergic rhinitis. It is a very effective drug, but has the inconvenient factor of being insoluble in water. Cyclodextrins were used to improve this limitation because of their ability to form inclusion complexes with guest drug molecules as well as increase the stability and bioavailability of the drugs. A rapid and simple HPLC method was developed to detect and quantify fluticasone propionate in inhalation particles on several matrices. Liquid chromatography with a UV detector at a wavelength of 236 nm, using a C18 column, was employed in this study. Isocratic elution was employed using a mixture of acetonitrile and water (60:40, v/v). The analytical method validation was performed in accordance with ICH guidelines, which included selectivity, range, linearity, accuracy, detection limit, quantitation limit, precision, robustness, and stability of solutions. This method showed to be selective and specific. Acceptable assay precision and accuracy (100 ± 5.0%) were obtained at 50– 150% of the analytical concentration of fluticasone propionate at the target concentration of 0.060 mg/mL, and good linearity (0.9958) was achieved over a range of 0.03 to 0.09 mg/mL for fluticasone propionate. The proposed HPLC method proved to be reliable. The validation and application of this method can be adopted for determining the fluticasone propionate in: assays, impingers and impactors, diffusion cells, dissolutions, and other tests. In addition, this method can be adapted and used in the pharmaceutical industry for routine analysis.     

沙美特罗替卡松治疗中重度支气管哮喘患者的疗效观察

目的观察沙美特罗替卡松治疗中重度支气管哮喘患者的临床疗效。方法 78例中重度支气管哮喘患者随机分为2组,对照组（n=38例）采用常规方法治疗;观察组（n=40例）采用沙美特罗替卡松治疗,2组疗程均为2周。比较2组治疗总有效率及肺功能指标变化情况。结果观察组治疗总有效率（82.5%）明显高于对照组（68.4%）（P〈0.05）;2组治疗后FEV1和FEV1/FVC肺功能情况均明显缓解（P〈0.05）,而观察组改善更为显著（P〈0.05）。结论沙美特罗替卡松治疗中重度支气管哮喘可明显改善临床症状,提高肺功能,值得临床推广应用。     

复方丙酸氯倍他索软膏联合二氧化碳点阵激光对增生性瘢痕患者VSS评分及复发率的影响

目的探讨复方丙酸氯倍他索软膏联合二氧化碳(CO2)点阵激光治疗增生性瘢痕(HS)患者的临床效果.方法选取2017年7月~2018年6月我院HS患者60例,按随机数字表法分为试验组(n=30)与对照组(n=30),对照组予以复方丙酸氯倍他索软膏,试验组予以复方丙酸氯倍他索软膏联合CO2点阵激光.对比两组疗效、不良反应发生率,记录两组治疗前后温哥华瘢痕量表(VSS)、视觉模拟评分法(VAS)评分及血清血管内皮生长因子(VEGF)、转化生长因子-β(TGF-β)水平;随访1年,对比两组复发率.结果试验组总有效率96.67%(29/30)较对照组80.00%(24/30)高(P<0.05);治疗后,试验组VSS、VAS评分较对照组低(P<0.05);治疗后,试验组血清VEGF、TGF-β水平较对照组低(P<0.05);试验组不良反应发生率10.00%(3/30)与对照组6.67%(2/30)对比无显著差异(P>0.05);试验组复发率3.70%(1/27)较对照组23.81%(5/21)低(P<0.05).结论复方丙酸氯倍他索软膏联合CO2点阵激光治疗HS患者效果显著,可减轻疼痛,下调血清VEGF、TGF-β水平,促使瘢痕恢复,降低复发率,且未明显增加不良反应发生率,值得临床推广应用.     

丙酸睾酮对大鼠坐骨神经损伤的治疗作用

目的:探讨雄激素丙酸睾酮(TP)对坐骨神经损伤的治疗作用及其机制.方法:雄性Wistar大鼠60只,随机等分为实验(TP)组(雄激素治疗组)和对照组(生理盐水治疗组),每组30只.建立坐骨神经离断后缝合外膜的损伤模型,分别在术后第4周、12周比较实验组与对照组运动神经传导速度(MNCV)恢复率和腓肠肌复合动作电位波幅(CMAP)恢复率;取损伤远端神经,观察再生神经的组织学变化;透射电镜观察超微结构变化;计算再生有髓神经纤维计数恢复率.结果:术后第4周,TP组MNCV恢复率为(26.74±6.54)%,CMAP恢复率为(28.58±4.49)%,对照组MNCV恢复率为(19.71±4.34)%,CMAP恢复率为(18.95±5.51)%,2组比较差异有统计学意义(P＜0.05);术后第12周,TP组MNCV恢复率为(54.31±12.89)%,CMAP恢复率为(71.24±4.05)%,对照组MNCV恢复率为(40.23±10.00)%,CMAP为(62.95±4.89)%,2组比较差异有统计学意义(P＜0.05);再生有髓纤维计数恢复率术后第4周TP组为(51.67±9.32)%,对照组为(34.04±10.86)%,差异有统计学意义(P＜0.05);术后第12周TP组为(84.03±3.84)%,对照组为(75.13±6.58)%,差异有统计学意义(P＜0.05).术后第4周、12周实验组再生神经纤维较对照组髓鞘致密,排列规则.结论:TP能促进周围神经再生和生理功能恢复.     

Effectiveness of perampanel in managing chronic pain caused by the complex regional pain syndrome: A case report

Rationale:The α-amino-3-hydroxy-5-methy-4-isoxazole propionate (AMPA) receptor plays a critical role in the development and persistence of pain, and AMPA receptor antagonists are considered possible therapeutic targets for controlling pain. This report describes a patient with complex regional pain syndrome (CRPS) type I in the right lower leg and foot who responded well to perampanel, an AMPA receptor antagonist, for managing the chronic pain.Patient concern:A 61-year-old woman complained of pain in her right lower leg and foot over a period of 7 year (numeric rating scale: 8) due to CRPS type I.Diagnosis:CRPS type 1.Interventions:Despite the combination of 300 mg pregabalin, 225 mg/1950 mg tramadol/acetaminophen, and 10 mg nortriptyline per day, her right lower leg and foot were nearly disabled due to the severity of the pain. High-dose prednisolone was found to be ineffective. Then, perampanel (4 mg; 2 mg twice) was administered to this patient daily.Outcomes:The day after treatment with perampanel, her pain completely disappeared. Additionally, at day 7 and 1 month follow-up, she reported no pain in the right lower leg and foot. Moreover, no adverse effects were reported after the application of perampanel.Lessons:These results suggest that perampanel may potentially be used to treat centralized pain.     

Ammonia metabolism,the brain and fatigue; revisiting the link

This review addresses the ammonia fatigue theory in light of new evidence from exercise and disease studies and aims to provide a view of the role of ammonia during exercise. Hyperammonemia is a condition common to pathological liver disorders and intense or exhausting exercise. In pathology, hyperammonemia is linked to impairment of normal brain function and the onset of the neurological condition, hepatic encephalopathy. Elevated blood ammonia concentrations arise due to a diminished capacity for removal via the liver and lead to increased exposure of organs, such as the brain, to the toxic effects of ammonia. High levels of brain ammonia can lead to deleterious alterations in astrocyte morphology, cerebral energy metabolism and neurotransmission, which may in turn impact on the functioning of important signalling pathways within the neuron. Such changes are believed to contribute to the disturbances in neuropsychological function, in particular the learning, memory, and motor control deficits observed in animal models of liver disease and also patients with cirrhosis. Hyperammonemia in exercise occurs as a result of an increased production by contracting muscle, through adenosine monophosphate (AMP) deamination (the purine nucleotide cycle) and branched chain amino acid (BCAA) deamination prior to oxidation. Plasma concentrations of ammonia during exercise often achieve or exceed those measured in liver disease patients, resulting in increased cerebral uptake. In this article we propose that exercise-induced hyperammonemia may lead to concomitant disturbances in brain function, potentially through similar mechanisms underpinning pathology, which may impact on performance as fatigue or reduced function, especially during extreme exercise.     

从运动神经元的TDP-43蛋白表达和ADAR2活性探讨肌萎缩侧索硬化症的发病机制

肌萎缩性侧索硬化症(ALS)是以上下两级运动神经元进行性丢失为特征的神经系统变性疾病,是运动神经元病(MND)中最常见的类型。运动神经元中的病理性TDP-43是ALS的病理特征。此外,散发性ALS运动神经元中作用于RNA的次黄嘌呤腺苷脱氢酶(ADAR2)减少、具有未经编辑Q/R位点的谷氨酸受体2(GluR2)表达增加,α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体(AMPAR)属性受影响,Ca2+通透性增加,Ca2+流入胞质增加导致神经元死亡。ALS运动神经元死亡包含病理性TDP-43和ADAR2活性下降,两种病理变化可能在细胞死亡中存在一定联系。ADAR2 mRNA是TDP-43蛋白的靶RNA,TDP-43蛋白在ADAR2的表达中起调节作用。近年来,研究者探讨ALS的基因治疗可能性:动物实验结果提示,外周静脉给予9型腺相关病毒载体(AAV9),可上调鼠运动神经元ADAR2,引发外源性ADAR2在中枢神经元表达,从而有效防治运动功能障碍。运动神经元的获救可能与TDP-43基因的正常表达有关。AAV9介导的ADAR2基因植入可能为ALS的基因治疗提供新的前景。