Bottom-Up and Top-Down Approaches to Explore Sodium Dodecyl Sulfate and Soluplus on the Crystallization Inhibition and Dissolution of Felodipine Extrudates

The objectives of this study were to explore sodium dodecyl sulfate (SDS) and Soluplus on the crystallization inhibition and dissolution of felodipine (FLDP) extrudates by bottom-up and top-down approaches. FLDP extrudates with Soluplus and SDS were prepared by hot melt extrusion, and characterized by polarized light microscopy, differential scanning calorimetry, and fourier transform infrared spectroscopy. Results indicated that Soluplus inhibited FLDP crystallization, and the whole amorphous solid dispersions (ASDs) were binary FLDP-Soluplus (1:3) and ternary FLDP-Soluplus-SDS (1:2:0.15～0.3 and 1:3:0.2～0.4) extrudates. Internal SDS (5%-10%) decreased glass transition temperatures of FLDP-Soluplus-SDS ternary ASDs without presenting molecular interactions with FLDP or Soluplus. The enhanced dissolution rate of binary or ternary Soluplus-rich ASDs in the nonsink condition of 0.05% SDS was achieved. Bottom-up approach indicated that Soluplus was a much stronger crystal inhibitor to the supersaturated FLDP in solutions than SDS. Top-down approach demonstrated that SDS enhanced the dissolution of Soluplus-rich ASDs via wettability and complexation with Soluplus to accelerate the medium uptake and erosion kinetics of extrudates, but induced FLDP recrystallization and resulted in incomplete dissolution of FLDP-rich extrudates. In conclusion, top-down approach is a promising strategy to explore the mechanisms of ASDs' dissolution, and small amount of SDS enhances the dissolution rate of polymer-rich ASDs in the nonsink condition.     

他克莫司与甲氨蝶呤联合治疗难治性类风湿关节炎效果观察

摘 要 目的：探讨他克莫司与甲氨蝶呤联合治疗难治性类风湿关节炎的临床效果。方法：80例难治性类风湿关节炎患者随机分为观察组和对照组,每组40例。观察组给予他克莫司与甲氨蝶呤联合治疗,对照组给予环磷酰胺与甲氨蝶呤联合治疗,两组均治疗24周。观察两组患者治疗前后关节疼痛指数、关节肿胀指数及晨僵时间的变化,采用视觉模拟评分（VAS ）对患者疼痛情况进行评估;评价两组临床疗效;比较两组患者治疗前后红细胞沉降率（ESR）、C 反应蛋白（CRP）、肿瘤坏死因子α（TNF α）、血管内皮生长因子（VEGF）等指标变化。结果：观察组总缓解率为100.00%,显著高于对照组的67.50%（P<0.05）。治疗后两组关节疼痛指数、关节肿胀指数、晨僵时间及VAS 评分均较治疗前显著降低（P<0.05）,且观察组各项指标均明显低于对照组（P<0.05）。两组治疗后ESR、CRP、TNF α、VEGF均较治疗前显著降低（P<0.05）,且观察组明显低于对照组（P<0.05）。结论：他克莫司与甲氨蝶呤联合治疗难治性类风湿关节炎临床疗效好,安全性高,其作用机制可能与降低患者体内炎症反应及下调VEGF水平有关。     

2012～2017年我州土家族及汉族患者药品不良反应分析

摘 要 目的：探讨恩施地区药品不良反应发生特点及土家族与汉族发生抗菌药物不良反应（ADR）的差异。方法：选取2012年1月～2017年7月恩施地区上报的ADR报告,从患者一般情况、ADR严重程度及发生时间、β 内酰胺类ADR、给药途径及ADR转归等方面,比较土家族及汉族患者发生的ADR的差异。结果：土家族与汉族患者发生的ADR,在β 内酰胺类尤其是头孢菌素类药物所致ADR分布、口服与静脉滴注用药分布,以及ADR转归情况等方面的差异有统计学意义（P<0.01）。两者发生ADR严重程度无差异（P﹥0.05）。结论：ADR的发生存在种族差异,少数民族地区在使用抗菌药物及给药途径方面应关注民族差异,减少ADR发生。     

The quality of life in Chinese population with chronic non-communicable diseases according to EQ-5D-3L: a systematic review

Purpose

Over the past decade, a changing spectrum of disease has turned chronic non-communicable diseases (CNCDs) into the leading cause of death worldwide. During the 2015 in China, there were more than 6.6 million deaths from NCDs, which was the highest rate around the world. In the present study, we performed a systematic review to analyze the health-related quality of life (HRQoL) according to EQ-5D-3L instrument in patients with different kinds of CNCDs in China.

Methods

We searched PubMed, Embase, Web of Science, Cochrane Library, VIP, WanFang Data, and CNKI databases up to April 12, 2018, to identify all relevant studies that reported on HRQoL assessed by EQ-5D-3L instrument in Chinese patients with CNCDs. Expert consultation and hand-searching of reference lists from retrieved studies were employed to identify additional references. The variation of mean utility values, EQ-VAS score ranges, and responses for each EQ-5D dimension described in relevant studies were extracted.

Results

A total of 5027 English-language articles and 618 Chinese-language articles were identified, among which 38 articles met full inclusion criteria. These 38 studies involved 18 kinds of CNCDs. In this review, the health utility for diabetes mellitus ranged from 0.79 to 0.94 (EQ-5D VAS scores from 61.5 to 78.6), hypertension from 0.78 to 0.93 (70.1–77.4), coronary heart disease from 0.75 to 0.90 (71.0–77.0), chronic obstructive pulmonary disease from 0.64 to 0.80 (55.0–67.0), epilepsy from 0.83 to 0.87 (78.3–79.6), cerebral infarction from 0.51 to 0.75 (49.7–79.0), while children cerebral palsy was 0.44 (27.3).

Conclusions

EQ-5D-3L is widely used in studies of HRQoL associated with CNCDs in China. Our results suggest that many factors may influence the measurement results of health utilities, including age, gender, sample source, comorbidities, rural/urban, and EQ-5D-3L value sets.

     

我国成年人群年龄对体质指数与高血压发病风险的修饰效应

目的 探讨中国成年人群年龄对BMI与高血压发病风险的影响。方法 采用整群随机抽样方法,选择河南省新安县≥ 18岁20 194名农村常住居民为研究对象,于2007-2008年开展基线调查,2013-2014年随访。采用logistic回归模型分析基线BMI、年龄别BMI与高血压发病风险的关系。结果 共纳入9 768名研究对象,在6年随访期内,发生高血压1 950例,其中男性784例,女性1 166例,相应的累积发病率分别为19.96%、20.51%和19.61%。以BMI<22 kg/m²组为参照,基线BMI为22~、24~、26~、≥ 28 kg/m²的研究对象发生高血压的RR值（95%CI）分别为1.09（0.93~1.27）、1.17（1.01~1.37）、1.34（1.14~1.58）和1.31（1.09~1.56）。青中年人群随着BMI的升高,高血压发病风险呈逐渐上升趋势（P<0.05）;老年人群随着BMI的增加,高血压发病风险则无显著变化趋势（P>0.05）。结论 BMI与高血压发病风险的关联受到年龄因素修饰的影响,在青中年人群中干预BMI可更有效降低高血压发病风险。     

镁基植入体植入兔股骨后周围骨微结构变化趋势

目的研究镁基植入体植入兔股骨不同时间点周围骨微结构参数的变化规律。方法将直径2 mm、长7 mm有螺纹及无螺纹的高纯镁(99.99 wt.%)钉植入兔股骨髁,对照组为钻孔组及健康组。在术后8、12、16周进行Micro-CT扫描和分析,得到各组微结构参数,包括:骨质密度(BMD)、骨体积分数(BV/TV)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)、骨小梁分离度(Tb.Sp)。结果 8周时无螺纹镁钉组BMD、BV/TV显著高于健康组,Tb.N显著高于钻孔组与健康组,Tb.Sp显著低于健康组;12周时有螺纹镁钉组BMD、BV/TV、Tb.N显著高于钻孔组与健康组,Tb.Th显著高于健康者,Tb.Sp显著低于钻孔组与健康组;16周时无螺纹镁钉组的BMD、BV/TV、Tb.N显著高于钻孔组与健康组,Tb.Sp显著低于钻孔组与健康组。结论镁基植入体促使周围骨组织的BMD、BV/TV、Tb.Th、Tb.N更高,Tb.Sp更低,说明其骨整合与骨生长状况良好,镁基植入体能有效促进骨再生。研究结果为镁基植入体的骨科临床应用提供理论依据。