Fraxinol attenuates LPS-induced acute lung injury by equilibrating ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas and inhibiting NLRP3

ContextAcute lung injury (ALI) is a serious heterogenous pulmonary disorder. Fraxinol was selected for this study since it is a simple coumarin compound, not previously investigated in ALI.ObjectivesThis study investigates the ALI therapeutic effect and mechanisms of fraxinol.Materials and methodsMale BALB/c mice were treated with fraxinol (20, 40, and 80 mg/kg) following intranasal injection of lipopolysaccharide (LPS; 10 μg in 50 μL). The mice in control group were intratracheally injected with 50 μL phosphate buffered saline (PBS). Raw264.7 cells were treated with fraxinol by 100 ng/mL LPS for 6 h, then treated by different concentrations of fraxinol (5, 10, and 25 μM) for 48 h. Cells in control group were treated with PBS.ResultsFraxinol with doses of 20, 40, and 80 mg/kg significantly attenuated LPS-induced lung injury in mice (lung injury score, 10.4, 31.2, 50.3%). Fraxinol attenuated the apoptosis and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3 (NLRP3) activation induced by LPS (apoptosis, 18.3, 30.2, 55.6%; NLRP3, 30.0, 47.7, 63.6%). The anti-apoptosis and anti-inflammation effects of fraxinol were also confirmed in Raw264.7 cells (apoptosis, 38.8, 55.3, 68.9%; NLRP3, 20.6, 55.7, 73.9%).Discussion and conclusionThe anti-ALI effects of fraxinol maybe by equilibrating ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas axis and inhibiting NLRP3 inflammasome. Our research provides a candidate drug in the treatment of ALI.     

中医心理疗法联合柴胡疏肝散与催眠术疗法治疗神经症临床比较

目的 观察中医心理疗法联合柴胡疏肝散与催眠术治疗神经症的临床疗效.方法 治疗组54例,用中医心理疗法联合柴胡疏肝散加减治疗;对照组42例,实施催眠术治疗.以SDS(抑郁自评量表)、SAS(焦虑自评量表)为疗效评定工具,将两种治疗效果进行比较分析.结果 两组临床疗效有显著差异,并且治疗组长期疗效持久、稳定.结论 中医心理疗法联合柴胡疏肝散加减治疗神经症优于对照组.     

超声下两种颈内静脉置管法的比较

目的 超声下比较两种路径颈内静脉置管方法的准确性及并发症的发生率,寻找更安全、可靠的颈内静脉穿刺路径。方法 选择需行颈内静脉穿刺患者60例,随机分为传统中路法穿刺组(A组,n=30)与颈内静脉搏动点法穿刺组(B组,n=30)。观察颈总动脉直径(D1)、颈内静脉直径(D2)、颈总动脉和颈内静脉重叠覆盖率、穿刺路径距颈内静脉中心距离(D3)、穿刺路径距颈总动脉外侧距离(D4)及可能触及颈总动脉例数。结果 与A组比较,B组D3较小,差异有统计学意义(P<0.05);B组D4明显大于A组,差异有统计学意义(P<0.05)。结论 颈内静脉搏动点法行颈内静脉穿刺更准确,并发症发生率更低。     

糖尿病前期人群健康管理的研究思路

糖尿病前期人群是发展成为糖尿病的高危群体,在糖尿病前期进行干预是防止其进展为糖尿病的最佳阶段,故不断探讨及完善糖尿病前期人群健康管理的研究思路具有重要意义。本文提出以中医“治未病”理论为指导,对糟尿病前期人群作出健康风险评估、制定适宜的生活干预方式、给予个性化的健康指导,并归纳糖调节受损易患人群的体质特点,以期形成规范化的健康管理体系。     

“呬”字诀呼吸操对稳定期 COPD 患者生存质量的影响

目的：探讨“呬”字诀对稳定期COPD患者生存质量的影响。方法选取稳定期COPD患者63例,随机分为试验组（31例）和对照组（32例）,试验组在常规治疗和护理基础上进行3个月“呬”字诀呼吸操训练,对照组仅进行常规治疗和护理。待训练结束后,采用吸系统疾病特异性生存质量量表（ SGRQ）、医疗资源利用情况（住院次数、住院时间、访问急诊次数）等指标对两组患者的生存质量进行评价。结果经过3个月干预后,试验组SGRQ总分、活动领域、影响领域三者得分明显低于对照组（ P＜0.01）;住院次数、住院天数显著少于对照组患者（P＜0.01）。结论“呬”字诀简单易行,且能有效减少稳定期COPD患者住院次数、缩短住院时间,从而提高其生存质量,值得在临床、社区康复工作中推广、应用。     

眼部血管平滑肌瘤与平滑肌瘤

报告眼部血管平滑肌瘤１２例，平滑肌瘤２例，并作临床病理分析。本病临床特点是：①ＣＴ显示为圆或椭圆形边界清楚包块，部分病例有钙化斑存在。②手术时所见为一个圆或椭圆形、有包膜、紫红色肿块，与周围组织粘连及易出血。按组织病理学分类，血管平滑肌瘤可分为三个类型（海绵状型、静脉型、实体型），在部分病例标本中，三种类型可同时存在。     

Development of cyclosporin A-loaded hyaluronic microsphere with enhanced oral bioavailability

To develop a hyaluronic microsphere with the improved oral bioavailability of poorly water-soluble cyclosporin A (CsA), the microspheres were prepared with varying ratios of sodium hyaluronate (HA)/sodium lauryl sulfate (SLS)/CsA using a spray-drying technique. The effects of HA and SLS on the dissolution and solubility of CsA in microspheres were investigated. The CsA-microsphere prepared with HA/SLS/CsA at the ratio of 4/2/1 gave the highest solubility and dissolution rate of CsA among those formulae tested. As solubility and dissolution rate of CsA were increased about 17- and 2-fold compared to CsA powder, respectively, this CsA-microsphere was selected as an optimal formula for oral delivery in rats. The CsA-microsphere and Sandimmun neoral sol gave significantly higher blood levels compared with CsA powder alone. Moreover, the AUC, T(max) and C(max) values of CsA in CsA-microsphere were not significantly different from those in Sandimmun neoral sol in rats, indicating that CsA-microsphere was bioequivalent to the commercial product in rats. Our results demonstrated that the CsA-microsphere prepared with HA and SLS, with improved bioavailability of CsA, might have been useful to deliver a poorly water-soluble CsA.     

EGFR mutation types and abundance were associated with the overall survival of advanced lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors

BackgroundEpidermal growth factor receptor tyrosine kinases inhibitors (EGFR-TKIs) are currently recognized as the standard treatment for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations. Clinically found patients with different EGFR mutational status have different prognosis.MethodsA retrospective cohort study was performed to explore the relationship between EGFR mutations and abundance with patient survival by using patient data from the Affiliated Cancer Hospital of Zhengzhou University between January 2013 and November 2016. All patients involved in the present study had sensitive EGFR mutations [either exon 19 deletion (DEL) or exon 21 L858R] and treated by EGFR-TKIs. They were followed up every three months until lost or dead. Mutation abundance was calculated as the copies of EGFR mutation divided by copies of EGFR locus, and the cut-off values for 19DEL and L858R were 4.9% and 9.5%, respectively.ResultsTotal of 236 patients were included, comprising 116 (49.2%) patients with 19DEL mutation and 120 (50.8%) patients with L858R mutation. The median follow-up duration was 23.2 months (95% CI: 14.9–26.7 months). Overall survival (OS) was significantly longer in patients with 19DEL mutation (20.9 months, 95% CI: 17.7–24.1 months versus 17.0 months, 95% CI: 14.4–19.6 months in patients with L858R; P=0.008) and in patients with high mutation abundance (20.9 months, 95% CI: 18.3–23.5 months versus 13.0 months, 95% CI: 10.3–15.7 months in patients with low mutation abundance; P<0.001). Multivariate Cox regression including age, performance status and tumor stage revealed that longer OS was independently associated with 19DEL mutation (HR: 0.48, 95% CI: 0.39–0.67, P=0.033) and high mutation abundance (HR: 0.62, 95% CI: 0.50–0.79, P=0.027).ConclusionsEGFR mutation types and abundance was associated with the patients’ survival which might be used to predict the efficacy of targeted therapy by EGFR-TKIs.     

两种给药途径致痫大鼠海马神经元超微结构损伤及caspase-3的表达特征

为了观察两种给药途径致痫大鼠海马神经元超微结构的损伤及caspase-3的表达特征,本研究分别采用海人酸腹膜腔注射(A组)和尾静脉注射(B组)诱发大鼠癫痫持续状态(SE)。分别于SE终止后3、6、24、48和72h取海马,电镜观察神经元超微结构的变化,免疫组化方法检测caspase-3的表达。结果显示:两组大鼠均在SE后3h出现线粒体损伤,细胞核的改变出现于SE后24h。A组致痫的潜伏期为97min±11min,神经元以凋亡为主;B组为48min±13min,神经元以坏死为主。SE后6～24h,两组大鼠海马内caspase-3的表达由胞浆向胞核逐渐移位,且均在SE后6h明显增高,24h达顶峰;A组高表达持续至72h,B组在48h显著降低。上述结果提示,线粒体的损伤出现于SE的早期,且可能是神经元损伤的关键环节;致痫方法不同,神经元的死亡形式也不同;而caspase-3的激活是神经元凋亡和坏死的共同通路。     

选择性头部降温对胎羊缺血性脑损伤纹状体神经元凋亡和星形胶质细胞增殖的影响

目的研究选择性头部降温对缺血性脑损伤胎羊纹状体神经元凋亡和星形胶质细胞增殖的影响。方法胎羊于妊娠117~124d时通过双侧颈动脉阻塞30min造成双侧脑缺血损伤,损伤后将胎羊随机分为:损伤组(n=10)、2h低温组(损伤后2h开始亚低温治疗,n=7)和6h低温组(损伤后6h开始亚低温治疗,n=8),另设正常对照组(n=5)。通过冷循环水进行选择性头部降温,取脑组织用免疫组化法检测胎羊纹状体caspase-3(半胱天冬氨酸酶-3),GFAP(胶质纤维酸性蛋白)和PCNA(增殖细胞核抗原)的表达。结果①纹状体神经元凋亡:正常对照组中,caspase-3表达极少(11.00±13.77),损伤组caspase-3免疫阳性细胞为177.70±48.69,明显增加(P=0.000),损伤后2h治疗组(54.14±39.44,P=0.000)和损伤后6h治疗组(122.43±52.36,P=0.017)均能减少caspase-3免疫阳性细胞。②纹状体星形胶质细胞增殖:与正常对照组(163.40±21.98)相比,缺血性脑损伤组的GFAP免疫阳性细胞明显增多(433.25±66.69,P=0.000),损伤后2h开始亚低温治疗(219.50±35.31,P=0.000)和损伤后6h开始亚低温治疗(272.50±86.20,P=0.000)均能减少GFAP免疫阳性细胞。③纹状体PCNA阳性细胞的表达:在正常对照组中,PCNA免疫阳性细胞较少,为153.40±12.46,缺血性脑损伤组的PCNA免疫阳性细胞明显增多(353.70±45.60,P=0.000),损伤后2h开始亚低温治疗(187.14±26.26,P=0.000)和损伤后6h开始亚低温治疗(230.25±67.46,P=0.000)均能减少PCNA免疫阳性细胞。结论亚低温可以抑制纹状体神经元的凋亡和星形胶质细胞的增殖,该作用可能为选择性头部降温的脑保护作用机制之一。