Quantitative biokinetics of titanium dioxide nanoparticles after intratracheal instillation in rats: Part 3

The biokinetics of a size-selected fraction (70?nm median size) of commercially available and ⁴⁸V-radiolabeled [⁴⁸V]TiO₂ nanoparticles has been investigated in healthy adult female Wistar-Kyoto rats at retention time-points of 1?h, 4?h, 24?h, 7?d and 28?d after intratracheal instillation of a single dose of an aqueous [⁴⁸V]TiO₂-nanoparticle suspension. A completely balanced quantitative biodistribution in all organs and tissues was obtained by applying typical [⁴⁸V]TiO₂-nanoparticle doses in the range of 40–240?μg·kg^?1 bodyweight and making use of the high sensitivity of the radiotracer technique. The [⁴⁸V]TiO₂-nanoparticle content was corrected for residual blood retained in organs and tissues after exsanguination and for ⁴⁸V-ions not bound to TiO₂-nanoparticles. About 4% of the initial peripheral lung dose passed through the air-blood-barrier after 1?h and were retained mainly in the carcass (4%); 0.3% after 28?d. Highest organ fractions of [⁴⁸V]TiO₂-nanoparticles present in liver and kidneys remained constant (0.03%). [⁴⁸V]TiO₂-nanoparticles which entered across the gut epithelium following fast and long-term clearance from the lungs via larynx increased from 5 to 20% of all translocated/absorbed [⁴⁸V]TiO₂-nanoparticles. This contribution may account for 1/5 of the nanoparticle retention in some organs. After normalizing the fractions of retained [⁴⁸V]TiO₂-nanoparticles to the fraction that reached systemic circulation, the biodistribution was compared with the biodistributions determined after IV-injection (Part 1) and gavage (GAV) (Part 2). The biokinetics patterns after IT-instillation and GAV were similar but both were distinctly different from the pattern after intravenous injection disproving the latter to be a suitable surrogate of the former applications. Considering that chronic occupational inhalation of relatively biopersistent TiO₂-particles (including nanoparticles) and accumulation in secondary organs may pose long-term health risks, this issue should be scrutinized more comprehensively.     

2013-2015年宝鸡市中心医院不同年龄段住院患者病原菌的分布及耐药性分析

目的 了解宝鸡市中心医院不同年龄段患者的病原菌分布及对常用抗菌药物的耐药性.方法 将宝鸡市中心医院2013年1月—2015年12月病原菌培养阳性的住院患者,按照0~14岁、15~64岁、≥65岁分为3个不同的年龄阶段,对3个年龄段患者病原菌的分布及其耐药情况进行统计与分析.结果 共分离出病原菌4077株,主要来源于呼吸道和尿,其中革兰阳性菌702株,占17.2%,主要为葡萄球菌中的金黄色葡萄球菌、凝固酶阴性葡萄球菌和肠球菌中的粪肠球菌和屎肠球菌;革兰阴性菌3375株,占82.8%,主要为肠杆菌中的大肠埃希菌、肺炎克雷伯菌和非发酵菌中的铜绿假单胞菌、鲍曼不动杆菌.大肠埃希菌、铜绿假单胞菌、鲍曼不动杆菌、金黄色葡萄球菌及肠球菌等多种病原菌对抗菌药物的耐药率随着患者年龄的增长而增高.结论 不同年龄住院患者的病原菌分布及其耐药性有所不同,抗感染治疗时应充分考虑患者的年龄因素,合理使用抗菌药物.     

蒿甲醚对C57BL/Ks J-db/db小鼠糖脂代谢的影响

目的研究蒿甲醚对db/db小鼠糖脂代谢的影响。方法取8周龄雄性C57BL/KsJ-db/db小鼠,分为模型组(ig给予1%甲基纤维素)和蒿甲醚400、200、100、50组(分别ig给予400、200、100、50 mg/kg蒿甲醚+1%甲基纤维素),每组6只。另选6只雄性C57BL/KsJ-db/+小鼠为对照组,共给药4周。每2天测量小鼠体质量;每3天检测小鼠摄食量并评估平均每日摄食量及体质量变化;每2天测定小鼠饮水量;每3天测量小鼠尿量;每7天于禁食8 h后,尾静脉采血,用罗氏血糖仪及配套试纸分别测量小鼠空腹血糖。通过葡萄糖耐量试验(IPGTT)和胰岛素耐量试验(IPITT)评估小鼠对葡萄糖的耐受力及对胰岛素的敏感性,通过生化试剂盒测定小鼠血清总胆固醇(TC)、三酰甘油(TG)、游离脂肪酸(FFA)水平。HE染色法观察小鼠胰腺和肝脏的形态改变。Westernblotting法分析小鼠肝脏中AMP活化蛋白激酶(AMPK)、葡萄糖转运蛋白体4(GLUT-4)和胰岛素受体β(IRβ)蛋白的表达。结果与对照组比较,模型组小鼠的摄食量、摄水量、尿量均明显升高(P0.001)。与模型组比较,各剂量蒿甲醚均能显著降低小鼠摄水量及尿量(P0.01、0.001);蒿甲醚400、200、100 mg/kg均能显著降低小鼠体质量及摄食量,并呈剂量依赖性(P0.05、0.01);蒿甲醚400、200、100mg/kg均显著降低小鼠空腹血糖水平,减少IPGTT的曲线下面积(AUCs),改善小鼠的胰岛素抵抗(P0.01、0.001)。与对照组比较,模型组小鼠的TC、TG及FFA水平均显著升高(P0.05)。与模型组比较,蒿甲醚可显著降低小鼠血清中的TC、TG及FFA水平,并呈剂量依赖性(P0.05);可显著改善db/db小鼠的胰岛空泡变性和肝脂肪变性,使小鼠肝脏中的AMPK、GLUT-4及IRβ蛋白表达增加(P0.05)。随着干预时间的延长,剂量越高的小鼠呈现出较高的死亡率及不良反应发生率。结论蒿甲醚可显著改善糖尿病小鼠的高脂状态及胰岛素抵抗,治疗脂肪肝,可能通过AMPK途径上调GLUT-4以及IRβ蛋白的表达发挥作用,有望用于代谢综合征为主的2型糖尿病的治疗。但较高剂量蒿甲醚及较长时间应用会导致较多不良反应的发生。     

改变体位联合 CT 靶扫描对特殊部位肺结节的诊断价值

目的：探讨改变体位联合C T靶扫描技术在特殊部位肺结节诊断中的价值。方法对22例行常规胸部C T扫描发现的位于心脏旁和后肋膈角的肺结节患者,增加改变体位及CT 靶扫描,记录2种扫描方法所得的图像的信噪比（SNR）和对比信噪比（CNR）,从肺野充气膨胀程度、伪影严重程度、肺血坠积效应3方面主观评价图像质量,对比分析2种扫描方法对病灶CT征象的显示情况,评价医师对肺结节的诊断信心度,并进行统计学分析。结果与常规胸部CT 扫描靶重建相比,改变体位靶扫描的图像质量主观评分提高（P＜0．01）,图像的SNR和CNR增加（P＜0．05）,对病灶CT征象显示情况得分提高（P＜0．05）,诊断信心度增加（P＜0．01）。结论改变体位联合CT靶扫描技术可以使结节征象显示更清楚,应作为心脏旁和后肋膈角肺结节的最佳扫描方法。     

Metabolic syndrome does not always play a critical role in decreased GFR

Background There is a paucity of literature available as to the relationship between different levels of each metabolic syndrome (MetS) component and decreased GFR. In the present study, we aimed to demonstrate whether MetS always plays a critical role in decreased GFR. Methods A cross-sectional study was conducted between February 2010 and September 2012, with 75,468 adults enrolled undergoing measurements of blood pressure as well as tests of blood and urine samples. Univariate and multivariable logistic regression analyses were performed to estimate the odds ratio (OR) with 95% confidence intervals (CI), and the chi-square test was used for categorical variables and described as a percentage. Results Of the 75,468 participants, 350 (0.5%) subjects met criteria for the decreased GFR, with a mean age of 48.79?±?13.76?years. After adjustment for age, diastolic blood pressure and high-density lipoprotein were inversely related to decreased estimated glomerular filtration rate (eGFR) in multivariable analyses, with an OR (95% CI) of 0.57 (0.39–0.84) and 0.41 (0.24–0.72), respectively. The prevalence rate of CKD in critical group was 0.73% (154 of 21,127) and 0% (0 of 370) in noncritical group. In analysis stratified by the type of MetS components, the differences in noncritical group and the reference group were not statistically significant (χ^2?=^?1.349, p?>?0.05). Conclusions MetS does not always play a critical role in decreased GFR, with different levels of individual components of MetS exerting idiosyncratic effects in decreased eGFR. In fact, patients with abnormal body mass index, high triglycerides, and elevated fasting plasma glucose would not have impact on decreased GFR.     

不同处方复方丹参黏附微丸黏附性能的评价

目的考察不同处方复方丹参黏附微丸的黏附性能,从而筛选出黏附性能较为合适的处方。方法以壳聚糖、羟丙基甲基纤维素K100M(HPMCK100M)、卡波姆为黏附材料,制备不同处方的复方丹参黏附微丸,并对其黏附性能进行测定。体外黏附性能的测定采用了最小剥离力法即测定黏附微丸与猪小肠的剥离力,组织残留法即测定微丸在猪小肠的滞留数。体内黏附性能的测定采用了直接灌胃法,通过测定微丸在小肠各部位的滞留数目,计算其黏附指数。结果组织残留法试验结果在相同时间内黏附材料占比40%的微丸残留数目较黏附材料占比30%的微丸多,最小剥离力法试验结果表明黏附材料占比40%的微丸其最小剥离力较大,同组织残留法结果一致。体内黏附试验显示黏附材料占比40%的微丸其黏附指数较小,但在胃中有一定的滞留。结论当黏附材料总占比一致时,各处方之间黏附性能并没有显著性差异,黏附材料增加时其黏附性能也会增加,但会增加在胃中的滞留时间,可能会破坏方中的有效成分。     

芎柰抗骨关节炎有效部位研究

目的 研究川芎山柰抗关节炎作用的有效部位.方法 利用小鼠热板法、乙酸扭体法和二甲苯致小鼠耳廓肿胀模型,比较芎柰水提物、醇提物的抗炎镇痛作用;采用木瓜蛋白酶诱导大鼠骨关节炎模型,比较不同溶剂萃取物的抗炎作用.结果 在相同剂量下,芎柰醇提物镇痛作用较水提物强(P＜0.05);芎柰醇提物乙酸乙酯萃取物能有效减轻骨关节炎大鼠踝关节宽度和足趾肿胀(P＜0.01),显著降低血清IL-1β和NO水平(P＜0.01),改善其病理学改变.结论 芎柰醇提物具有明显的抗炎镇痛作用,其乙酸乙酯部位是芎柰抗关节炎的最有效部位.     

Exploring the feasibility of the use of biopolymers as a carrier in the formulation of amorphous solid dispersions – Part I: Gelatin

Biopolymers have rarely been used so far as carriers in the formulation of amorphous solid dispersions (ASD) to overcome poor solubility of active pharmaceutical ingredients (APIs). In an attempt to enlarge our knowledge on this topic, gelatin, type 50PS was selected. A screening study was initiated in which twelve structurally different poorly soluble biopharmaceutical classification system (BCS) Class II drugs (carbamazepine, cinnarizine, diazepam, itraconazole, nifedipine, indomethacin, darunavir (ethanolate), ritonavir, fenofibrate, griseofulvin, ketoconazole and naproxen) were selected for evaluation. Solid dispersions of five different drug loadings of these twelve compounds were prepared by lyophilization and evaluated for their solid state properties by mDSC and XR(P)D, and in vitro dissolution performance. Even without any process optimization it was possible to form either fully amorphous or partially amorphous systems, depending on the API and API to carrier ratio. Hence in this respect, gelatin 50PS behaves as any other carrier. Dissolution of the API from the solid dispersions significantly exceeded that of their crystalline counterparts. This study shows the potential of gelatin as a carrier to formulate amorphous solid dispersions.     

模糊物元模型评价当归不同提取部位的活血作用

目的：筛选当归活血的有效部位;探讨模糊物元模型在当归不同提取部位活血效果综合评价中的应用。方法：以皮下注射盐酸肾上腺素结合冰水浴建立急性大鼠血瘀模型,通过检测血液流变学及凝血4项[凝血酶原时间（PT）,活化部分凝血活酶时间（APTT）和凝血酶时间（TT）,纤维蛋白原含量（FIB）]指标,评价当归不同提取部位的活血效果;运用基于变异系数权重的模糊物元模型对活血的效果进行综合评价。结果：部位1~7均能降低大鼠全血黏度和血浆黏度,部位2能明显延长PT、TT时间（P<0.05）。反映活血总效应的最大贴进度值为0.527（70%乙醇浸渍部位）。结论：70%乙醇浸渍部位为当归活血的有效部位;基于变异系数权重的模糊物元模型可客观、准确地评价当归不同提取部位活血的综合效果。     

郑州市居民基本医疗保险不同参保人群健康公平性研究*

目的以不同参保人群为研究对象,分析评价居民健康状况及公平性,寻找存在的问题和不足,为政府和相关部门进一步深化医疗体制改革、完善现有医疗保险制度提供理论依据。方法运用集中指数法对不同参保人群的健康状况进行公平性分析评价。结果整体人群的两周患病及慢性病患病的集中指数分别为-0.018、0.056。不同参保人群在不同收入水平分层下的健康公平存在差异,两周患病集中指数分别为-0.031、-0.057和0.080,慢性病患病集中指数分别为-0.010、0.013和0.093。结论两周患病主要集中在收入水平较低的人群中,而慢性病患病主要集中在收入水平较高的人群中,城镇职工医保人群的健康不公平性差异较大。