慢性HBV携带小鼠模型评估

【摘要】 目的 研究琥珀酸美托洛尔普通颗粒与自制缓释微丸的药代动力学行为,并验证缓释微丸的缓释特性,为后期开展缓释制剂研究打下基础。方法 将大鼠随机分为普通组、缓释组各6只,每组雌雄各3只,普通组大鼠单次口服琥珀酸美托洛尔普通颗粒,缓释组大鼠单次口服等剂量的琥珀酸美托洛尔缓释微丸。采用LC MS/MS法测定血药浓度,采用DAS 2.1.1版药代动力学软件计算药代动力学参数,采用SPSS130统计学软件进行统计学分析。结果 结果表明,两种剂型的AUC(0 t) 、AUC(0 ∞) 、Cmax以及MRT(0 t)、MRT(0 ∞)、t1/2z、Tmax差异显著,具有统计学意义。结论 琥珀酸美托洛尔自制缓释微丸具有显著的缓释特性。可为新剂型的研制、开发提供资料参考。     

放射性125I粒子治疗晚期肺癌的疗效分析

目的 探讨晚期肺癌的放射性¹²⁵I粒子植入治疗的临床疗效。方法 收集自2012年1月至2015年12月经放射性¹²⁵I粒子植入治疗的肺癌患者186例,分析患者的疗效及生存率。结果 所有入组病例均临床随访36个月,失访5例,随访率97.31%。平均生存期16.9个月,中位生存时间18.0个月(8～23个月)。影像学随访至12个月,完全缓解(complete relief, CR)35例,部分缓解(partial relief, PR)78例,疾病稳定(stable disease, SD)32例,疾病进展(progress disease, PD)23例,死亡18例。疾病控制(CR+PR+SD)145例,12个月总体控制率77.96%,术后6例死于呼吸衰竭,12例死于全身转移、恶液质,术后最长存活时间23个月。3例粒子移位脱落至纵隔,3例出现少量气胸,经保守治疗自行吸收。5例咯血痰,经补液止血治疗后治愈。无胸腔积液、肺部感染或针道种植转移等并发症。结论 放射性¹²⁵I粒子植入在改善晚期肺癌患者生活质量的同时,提高了患者远期生存率,是一种安全、有效的治疗方法。     

热疗联合125I粒子治疗复发性直肠癌的近期疗效评价

目的：通过比较复发性直肠癌患者治疗前、后影像学和血清中癌胚抗原（CEA）以及术后随访结果,评价热疗联合¹²⁵I放射性粒子治疗直肠癌的有效性。方法：手术且放疗后行CT引导下¹²⁵I放射性粒子植入术（20例手术治疗患者,1例患者无法耐受热疗退出）,术前应用放射性粒子治疗计划系统（TPS）制定粒子植入计划,粒子间距为1.0 cm,植入后立即复查CT,再行剂量验证,植入粒子数量为12~58颗,每颗粒子放射性活度为0.5 mCi,肿瘤周边匹配剂量为90~140 Gy。射频热疗,每次60 min,维持温度43℃,每周2次,连续3周。治疗后随访3个月,通过影像学结果和血清中CEA水平变化评价有效率,并评估尿频、尿痛、血尿和直肠出血等并发症。结果：与治疗前比较,随访6个月后影像学结果显示肿瘤缩小;患者治疗后血清中CEA水平由治疗前（30.25±8.32） mg·L^-1降低到（11.89±5.22） mg·L^-1（t=13.158,P < 0.01）;局部有效率94.7%（18/19）,疼痛缓解率为94.4%（17/18）;治疗前NRS评分中位数为6（4,7）分,治疗后NRS评分中位数为1（0,3）分,治疗前后比较差异有统计学意义（P < 0.01）。随访期间患者未出现尿频、尿痛、血尿和直肠出血等并发症。结论：热疗联合¹²⁵I放射性粒子植入对复发性直肠癌具有较好的临床效果,是复发性直肠癌有效的综合治疗手段。     

磨损颗粒引发假体周围骨溶解的机制及药物治疗进展

目的对磨损颗粒引发假体周围骨溶解的机制及药物治疗进展进行了综述介绍。方法对国外近期相关文献进行综述。结果及结论人工关节置换是治疗晚期骨关节炎及老年股骨颈骨折的有效方法,能达到解除关节疼痛、重建活动功能及提高生活质量的目的。人工关节无菌性松动是影响人工关节使用寿命和远期疗效的最重要的并发症。磨损颗粒诱发假体周围组织细胞产生一系列生物学反应是导致假体周围骨溶解及假体无菌性松动的重要因素。磨损颗粒刺激假体周围的巨噬细胞、成骨细胞、成纤维细胞等产生多种细胞因子,形成破骨细胞性骨吸收,同时影响成骨细胞的分化及功能,抑制骨形成。药物在预防和治疗磨损颗粒引起的人工关节松动方面能起到积极的作用。     

清胰颗粒对重症急性胰腺炎大鼠肠黏膜上皮紧密连接的保护作用

目的：探讨清胰颗粒对重症急性胰腺炎（SAP）大鼠肠黏膜上皮紧密连接的保护作用。方法：24只健康雄性Wistar大鼠随机分为假手术组、SAP组和清胰颗粒组。采用3.5%牛磺胆酸钠胆胰管逆行注射制备SAP大鼠模型,清胰颗粒组于造模前2 h、造模后6 h和18 h分别给予清胰颗粒灌胃,SAP组以同样的方法给予安慰剂。各组分别于造模后24 h取末端回肠,HE染色,光镜下观察病理组织学改变,采用Chiu’小肠组织损伤评价标准对肠黏膜损伤进行评价,应用Western blot和实时荧光定量PCR法检测回肠黏膜上皮紧密连接蛋白（Occludin）表达。结果：与假手术组相比,SAP组大鼠Chiu’小肠组织损伤评分（4.6±0.6） vs （0.0±0.0）明显升高,与SAP组相比,清胰颗粒组Chiu’小肠组织损伤评分（2.0±0.4）vs（4.6±0.6）明显降低;Western blot和实时荧光定量PCR结果显示,与假手术组相比SAP组大鼠Occludin蛋白表达（1.2±0.4）vs（3.2±0.4）和mRNA表达（1.3±0.3）vs（2.9±0.5）明显降低（P＜0.05）;与SAP组相比,清胰颗粒组 Occludin蛋白表达（4.1±0.4）vs（1.2±0.4）和mRNA表达（4.2±0.3）vs（1.3±0.3）明显升高（P＜0.05）。结论：清胰颗粒能减轻SAP大鼠肠黏膜损伤程度,这一作用可能与增强肠黏膜紧密连接蛋白Occludin表达有关。     

Inhibitory effect of icariin on Ti-induced inflammatory osteoclastogenesis

Background

Wear particle-induced periprosthetic osteolysis that results in aseptic loosening is the most common cause of long-term failure after total joint replacement.

Materials and methods

Icariin (ICA), a flavonoid isolated from Epimedium pubescens, inhibits osteoclast formation, but its effects on wear particle-induced inflammatory osteoclastogenesis remains unclear. We investigated the role of ICA in the regulation of osteoclast differentiation in a murine macrophage cell line (RAW264.7), which is stimulated by titanium (Ti) particles and the receptor activator of NF-κB ligand.

Results

ICA effectively inhibited osteoclast formation and bone resorption in the differentiation medium. ICA (10⁻⁷ mol/L) significantly reduced the number of tartrate-resistant acid phosphatase-positive cells compared with the control, and significantly reduced the percentage of the surface covered by resorption lacunae. Quantitative real-time polymerase chain reaction analysis showed that ICA inhibited messenger RNA expression for the receptor activator of nuclear factor-κB, cathepsin K, tartrate-resistant acid phosphatase-positive, and matrix metalloproteinase-9 in RAW264.7 cells stimulated by Ti particles and receptor activator of NF-κB ligand. ICA also reduced pro-inflammatory cytokine expression of interleukin-1β and tumor necrosis factor-α in RAW264.7 cells cultured with Ti particles. In addition, incubation with cholecystokinin-8 showed that ICA had no toxic effects on RAW264.7 cells.

Conclusions

ICA possibly elicited inhibitory effects on inflammatory osteoclastogenesis induced by Ti particles, indicating that ICA may be useful for the prevention and treatment of wear particle-induced osteolysis.     

槐耳颗粒与索拉菲尼对于小肝癌切除术后的有效性及安全性分析

目的比较小肝癌切除术后服用槐耳颗粒或索拉菲尼的有效性及安全性。方法回顾性搜集我中心小肝癌患者行根治性手术切除后服用槐耳颗粒或索拉菲尼的82例患者,根据术后服用药物的不同分为槐耳颗粒组（51例）及索拉菲尼组（31例）,分析2组患者的术前人口学资料、术前肿瘤学特征及术后资料,比较2组患者的生存率、肿瘤复发率、服药后不良事件等。结果 1 2组患者的人口学资料、肝功能、肿瘤特点比较差异均无统计学意义（P〉0.05）。2槐耳颗粒组和索拉菲尼组的总生存率比较,差异无统计学意义（P=0.737）,无瘤生存率2组间比较差异也无统计学意义（P=0.699）。3肿瘤复发或转移在槐耳颗粒组有19例（37.3%）,而在索拉菲尼组有10例（32.3%）,2组的复发或转移发生率比较,差异无统计学意义（P=0.648）。4槐耳颗粒组共有6例次（5例）出现不良反应,其中恶心伴或不伴呕吐3例,疲劳2例,腹泻1例。索拉菲尼组共发生13例次（11例）不良反应,其中恶心伴或不伴呕吐2例,疲劳2例,腹泻4例,手足综合征2例,脱发1例,皮疹1例,高血压1例。索拉菲尼组不良反应发生率明显高于槐耳颗粒组（35.5%比9.8%,P=0.026）。结论对于已经行根治性切除的小肝癌来讲,槐耳颗粒以其良好的治疗效果及可靠的安全性,可以考虑作为一种有效的术后辅助治疗方法。     

风邪入侵与中药注射剂安全性*

本研究从词源角度得出“六淫”具有无形侵入性,分析出六淫之首的风邪的病因学基础是“虫”。继而结合现代认识,得出风邪之“虫”主要包含肉眼不可见的微生物和大分子颗粒物。而大分子颗粒物存在中药注射剂中,继而通过比较中药注射剂不良反应特点得出中药注射剂所致不良反应具有风邪属性,致病原为大分子杂质。本文还对风邪和中药注射剂不良反应的防治提出参考意见。     

超高分子聚乙烯颗粒刺激单核细胞高表达CD147/EMMPRIN

目的探讨不同浓度磨损颗粒对单核细胞表达细胞外基质金属蛋白酶诱导剂（CD147/EMMPRIN）的影响。方法根据颗粒/细胞比值实验分为0、1、10、100、500、1000共6组,将不同浓度的超高分子聚乙烯（UHMWPE）颗粒与人单核细胞株THP-1共培养24h,台盼蓝染色检测THP-1细胞存活率,利用流式细胞术、Real-time PCR和Western blot检测THP-1细胞CD147/EMMPRIN的表达。结果加入UHMWPE颗粒前及共培养24h后THP-1细胞存活率均大于90%。流式细胞术、Real-timePCR和Westernblot结果均显示加入UHMWPE颗粒后,CD147/EMMPRIN表达较对照组（即颗粒/细胞比值为0）增加,当颗粒/细胞比值在1-100范围时,CD147/EMMPRIN表达与颗粒浓度正相关,颗粒/细胞比值大于或等于100时,CD147/EMMPRIN稳定保持在高表达水平,不随颗粒浓度升高而变化。结论 UHMWPE颗粒刺激单核细胞高表达CD147/EMMPRIN,并呈浓度依赖性。     

Microglia mediate diesel exhaust particle-induced cerebellar neuronal toxicity through neuroinflammatory mechanisms

In addition to the well-established effects of air pollution on the cardiovascular and respiratory systems, emerging evidence has implicated it in inducing negative effects on the central nervous system. Diesel exhaust particulate matter (DEP), a major component of air pollution, is a complex mixture of numerous toxicants. Limited studies have shown that DEP-induced dopaminergic neuron dysfunction is mediated by microglia, the resident immune cells of the brain. Here we show that mouse microglia similarly mediate primary cerebellar granule neuron (CGN) death in vitro. While DEP (0, 25, 50, 100 μg/2 cm²) had no effect on CGN viability after 24 h of treatment, in the presence of primary cortical microglia neuronal cell death increased by 2–3-fold after co-treatment with DEP, suggesting that microglia are important contributors to DEP-induced CGN neurotoxicity. DEP (50 μg/2 cm²) treatment of primary microglia for 24 h resulted in morphological changes indicative of microglia activation, suggesting that DEP may induce the release of cytotoxic factors. Microglia-conditioned medium after 24 h treatment with DEP, was also toxic to CGNs. DEP caused a significant increase in reactive oxygen species in microglia, however, antioxidants failed to protect neurons from DEP/microglia-induced toxicity. DEP increased mRNA levels of the pro-inflammatory cytokines IL-6 and IL1-β, and the release of IL-6. The antibiotic minocycline (50 μM) and the peroxisome proliferator-activated receptor-γ agonist pioglitazone (50 μM) attenuated DEP-induced CGN death in the co-culture system. Microglia and CGNs from male mice appeared to be somewhat more susceptible to DEP neurotoxicity than cells from female mice possibly because of lower paraoxonase-2 expression. Together, these results suggest that microglia-induced neuroinflammation may play a critical role in modulating the effect of DEP on neuronal viability. .