Effects of synthetic and biological disease modifying antirheumatic drugs on lipid and lipoprotein parameters in patients with rheumatoid arthritis

BackgroundDyslipidemia in rheumatoid arthritis (RA) patients is frequently observed, and treatment with anti-rheumatic drugs has an impact on lipid profiles. Pathophysiologically, inflammation leads to decreased blood lipids and lipoproteins; RA treatment reduces inflammation and therefore may increase lipids and lipoproteins. Whether the lipid changes with RA treatment confer an increased risk of cardiovascular disease or just reflect their potentially atheroprotective anti-inflammatory effect is currently unclear due to limited and conflicting data.ObjectiveThe aim of this review is to summarize the current knowledge on the effects of synthetic and biological disease modifying antirheumatic drugs for the treatment of RA on lipid and lipoprotein parameters.ResultsRecent studies on methotrexate emphasize its anti-atherogenic effect. Golimumab combined with methotrexate revealed a trend towards an anti-atherogenic potential. The known pro-atherogenic lipid-spectrum alterations caused by tofacitinib can be effectively treated with atorvastatin. Tocilizumab signals a favorable impact on the extent of lipid modifications when combined with methotrexate. Abatacept indicated a trend towards an anti-atherogenic lipid profile demonstrated by favorable effects on HDL-C and on the TC/HDL-C ratio. Rituximab has beneficial effects on HDL-C and ApoA1, as well as on the ApoB/ApoA1 ratio.Clinical implicationsAnti-rheumatic drugs have various effects on lipid parameters, which in part appear pro-atherogenic. However, because many of these lipid changes may well reflect their potentially atheroprotective anti-inflammatory action the cardiovascular impact of these changes remains unclear. Whatsoever, cardiovascular safety trials for antirheumatic drugs would be valuable.     

A highly tumor-targeted nanoparticle of podophyllotoxin penetrated tumor core and regressed multidrug resistant tumors

Podophyllotoxin (PPT) exhibited significant activity against P-glycoprotein mediated multidrug resistant (MDR) tumor cell lines; however, due to its poor solubility and high toxicity, PPT cannot be dosed systemically, preventing its clinical use for MDR cancer. We developed a nanoparticle dosage form of PPT by covalently conjugating PPT and polyethylene glycol (PEG) with acetylated carboxymethyl cellulose (CMC-Ac) using one-pot esterification chemistry. The polymer conjugates self-assembled into nanoparticles (NPs) of variable sizes (20–120 nm) depending on the PPT-to-PEG molar ratio (2–20). The conjugate with a low PPT/PEG molar ratio of 2 yielded NPs with a mean diameter of 20 nm and released PPT at ∼5%/day in serum, while conjugates with increased PPT/PEG ratios (5 and 20) produced bigger particles (30 nm and 120 nm respectively) that displayed slower drug release (∼2.5%/day and ∼1%/day respectively). The 20 nm particles exhibited 2- to 5-fold enhanced cell killing potency and 5- to 20-fold increased tumor delivery compared to the larger NPs. The biodistribution of the 20 nm PPT-NPs was highly selective to the tumor with 8-fold higher accumulation than all other examined tissues, while the larger PPT-NPs (30 and 120 nm) exhibited increased liver uptake. Within the tumor, >90% of the 20 nm PPT-NPs penetrated to the hypovascular core, while the larger particles were largely restricted in the hypervascular periphery. The 20 nm PPT-NPs displayed significantly improved efficacy against MDR tumors in mice compared to the larger PPT-NPs, native PPT and the standard taxane chemotherapies, with minimal toxicity.     

F形空心钉与传统3枚平行钉治疗Pauwels Ⅲ型股骨颈骨折的疗效比较

目的:分析比较"F"形空心钉与传统倒三角3枚平行螺钉内固定治疗青壮年Pauwels Ⅲ型股骨颈骨折的临床疗效。方法：2017年1月至2020年1月收治Pauwels Ⅲ型股骨颈骨折患者38例，根据置入钉方式的不同将其分为两组，其中A组18例，采用"F"形空心钉固定，男12例，女6例，年龄37~55岁，受伤至手术时间1~3 d。B组20例，采用传统倒三角3枚平行拉力螺钉固定，男12例，女8例，年龄35~55岁，受伤至手术时间为1~3 d。比较两组患者骨折不愈合，股骨头坏死，股骨颈短缩，空心螺钉退出情况，髋关节功能Harris评分，疼痛视觉模拟评分（visual analogue scale，VAS）。结果：所有患者获得随访，时间为15~31个月。两组患者在骨折不愈合，股骨颈短缩，股骨头坏死方面差异无统计学意义（P>0.05）；两组患者在螺钉退出方面差异有统计学意义（P<0.05）。两组患者术后12个月时髋关节Harris评分及VAS评分差异均无统计学差异（P>0.05）。结论："F"形与传统倒三角3枚平行空心钉内固定治疗青壮年Pauwels Ⅲ型股骨颈骨折中短期疗效相似，但"F"形空心钉退钉率较低。     

2例胰岛素自身免疫综合征临床病例分析

通过回顾分析我院2例确诊为胰岛素自身免疫综合征(IAS)患者的临床资料,并复习相关文献,总结发病机制及治疗方法,探讨IAS患者的临床特点,提高对低血糖症的诊治水平。     

坎地沙坦酯联合氢氯噻嗪治疗中重度高血压的临床疗效比较

目的 分析中重度高血压应用坎地沙坦酯或贝那普利与氢氯噻嗪联合治疗的临床疗效情况。 方法 选择蚌埠医学院第二附属医院2016年6月—2018年7月诊治的86例高血压患者，按照随机数字表分成研究组(43例)与对照组(43例),对照组使用贝那普利(规格:10 mg*10片，开始剂量为每次5 mg，每日1次)联合氢氯噻嗪(规格:25 mg*100片，开始剂量为每次25 mg，每日1次)治疗，研究组予以坎地沙坦酯(规格:4 mg*14片，起始剂量每日1次，每次8 mg)结合氢氯噻嗪治疗，观察并比较2组患者血压、血钾与肾功能、不良反应情况。 结果 治疗前，2组血压指标差异无统计学意义(P＞0.05)；治疗后，2组舒张压、收缩压均有改善(P＜0.05)，且研究组舒张压(77.42±8.53)mm Hg、收缩压(121.31±15.84) mm Hg等血压指标改善情况显著优于对照组(P＜0.05)；研究组尿酸水平为(368.46±98.79)μmol/L，低于对照组的(412.36±102.14)μmol/L，差异有统计学意义(P＜0.05)，研究组出现低血钾症、头痛等不良反应的概率(6.98%)明显低于对照组(23.26%)，比较差异具有统计学意义(P＜0.05)。 结论 与贝那普利结合氢氯噻嗪相比，坎地沙坦酯与氢氯噻嗪结合应用对中重度高血压的疗效更佳，可明显控制血压水平，保护肾功能，且不良反应少。      

创伤后重型急性弥漫性脑肿胀临床治疗策略

目的 探讨重型创伤后急性弥漫性脑肿胀（PADBS）患者保守治疗与手术治疗的疗效。方法 分析 2016年1月—2019年12月该院神经外科收治的44例重型PADBS患者，根据治疗方式分为手术组和保守治疗组，统计入院时格拉斯哥昏迷量表（GCS）评分、头颅CT检查情况、伤后6个月格拉斯哥预后量表（GOS）评分等资料。结果 两组患者入院时年龄、性别及GCS评分比较，差异无统计学意义（P>0.05）。两组患者伤后6个月时GOS评分比较，差异无统计学意义（P>0.05），但两组住院时间比较，差异有统计学意义（P<0.05），手术组长于保守治疗组。结论 重型PADBS在无瞳孔变化及GCS评分下降的情况下，可密切观察病情下选择保守治疗。