心脑宁胶囊治疗血脂代谢异常的临床疗效及安全性观察

目的：观察心脑宁胶囊治疗血脂代谢异常的临床疗效及安全性。方法将86例血脂代谢异常的患者随机分为治疗组（44例）和对照组（42例）。两组均予相同的基础治疗,对照组加用辛伐他汀（40 mg,晚间服）,治疗组加用心脑宁胶囊（每次3粒,每日3次）,1个疗程均为12周,观察记录治疗前后血脂指标及症状积分的变化。结果治疗组总有效率为88.6%,显著高于对照组（69.0%,掊2=6.58,P<0.01）。治疗后治疗组TC、TG、LDL-C的降低程度显著优于对照组,HDL-C升高程度显著优于对照组,差异均有统计学意义（P<0.05）。治疗组症状积分改善情况优于对照组（掊2=9.89,P<0.01）。治疗组未出现毒副反应。结论心脑宁胶囊改善血脂代谢指标疗效显著、安全可靠,且能更好地减轻临床症状。     

Liver fat accumulation measured by high-speed T2-corrected multi-echo magnetic resonance spectroscopy can predict risk of cholelithiasis

BACKGROUND Liver fat accumulation is associated with increased cholesterol synthesis and hypersecretion of biliary cholesterol, which may be related to the development of cholelithiasis.AIM To investigate whether liver fat accumulation measured by high-speed T2-corrected multi-echo magnetic resonance spectroscopy(MRS) is a risk factor for cholelithiasis.METHODS Forty patients with cholelithiasis and thirty-one healthy controls were retrospectively enrolled. The participants underwent high-speed T2-corrected multi-echo single-voxel MRS of the liver at a 3 T MR scanner. The proton density fat fraction(PDFF) and R~2 value were calculated. Serum parameters and waist circumference(WC) were recorded. Spearman's correlation analysis was used to analyze the relationship between PDFF, R~2, and WC values. Multivariate logistic regression analysis was carried out to determine the significant predictors of the risk of cholelithiasis. Receiver operating characteristic curve(ROC) analysis was used to evaluate the discriminative performance of significant predictors.RESULTS Patients with cholelithiasis had higher PDFF, R~2, and WC values compared with healthy controls(5.8% ± 4.2% vs 3.3% ± 2.4%, P = 0.001; 50.4 ± 24.8/s vs 38.3 ±8.8/s, P = 0.034; 85.3 ± 9.0 cm vs 81.0 ± 6.9 cm, P = 0.030; respectively). Liver iron concentration extrapolated from R~2 values was significantly higher in the cholelithiasis group(2.21 ± 2.17 mg/g dry tissue vs 1.22 ± 0.49 mg/g dry tissue, P = 0.034) than in the healthy group. PDFF was positively correlated with WC(r = 0.502, P 0.001) and R~2(r = 0.425, P 0.001). Multivariate logistic regression analysis showed that only PDFF was an independent risk factor for cholelithiasis(odds ratio = 1.79, 95%CI: 1.22-2.62, P = 0.003). ROC analysis showed that the area under the curve of PDFF was 0.723 for discriminating cholelithiasis from healthy controls, with a sensitivity of 55.0% and specificity of 83.9% when the cut-off value of PDFF was 4.4%.CONCLUSION PDFF derived from high speed T2-corrected multi-echo MRS can predict the risk of cholelithiasis.     

雌二醇下调铁对成骨细胞活性的抑制作用

目的了解雌二醇与铁对小鼠原代成骨细胞活性的影响及活性氧(ROS)的作用。方法提取新生小鼠颅骨原代成骨细胞,经差速贴壁法纯化后传代,选取3~4代进行实验,随机分为对照组,枸橼酸铁铵(FAC)组和FAC+17β-雌二醇(FAC+E2)组,分别用2.5μmol/L FAC和10 nmol/L E2干预7 d后收集细胞,用CCK-8法检测各组细胞增殖情况;用碱性磷酸酶(ALP)活性试剂盒检测各组细胞碱性磷酸酶活性;荧光定量PCR(Q-PCR)检测成骨相关基因(Runx2、osterix、Bglap、IBSP)表达;荧光酶标仪检测各组ROS水平并在荧光显微镜下观察。结果细胞活性氧水平检测结果显示,FAC组活性氧水平明显高于其余各组,FAC+E2组与FAC组相比ROS水平降低(P0.05);FAC干预后细胞增殖能力及ALP活性明显下降(P0.05),FAC+E2组细胞增殖能力较FAC组上升(P0.05),ALP活性上升,但差异无统计学意义(P0.05);Q-PCR结果显示,与对照组相比,FAC组Runx2、osteorix表达水平明显下降(P0.05),FAC+E2组与FAC组相比,各基因表达水平均显著升高(均P0.05)。结论 FAC可能通过升高ROS水平抑制成骨细胞生物活性;雌二醇可能通过清除FAC诱导生成的ROS下调该抑制作用。     

子宫内膜异位症从蓄血证论治

[目的]探讨以《伤寒论》蓄血证理论治疗子宫内膜异位症的可行性。[方法]通过跟师学习,结合《伤寒论》中蓄血证相关理论,从病机、证候、治疗几方面阐述子宫内膜异位症与蓄血证之间的相互关系,并列举验案加以分析佐证。[结果]从临床角度看,蓄血证与子宫内膜异位症有相似之处,离经之血瘀滞,瘀热互结下焦是其病因病机,以少腹硬满胀痛、血下则缓为主要临床表现。破结逐瘀是其治疗大法,以抵当汤为治疗主方。临证施治时,根据月经周期、患者体质,在破结逐瘀泻热基础上,佐以补肾、健脾、温经、解痉,并配合针灸治疗。文中所附子宫内膜异位症病案,皆为瘀热互结下焦,从蓄血证论治,以水蛭、地鳖虫祛瘀消散离经之血,以大黄、猫爪草等泻热解毒,并防止病灶的异常出血,取得较好疗效。[结论]以《伤寒论》蓄血证理论治疗下焦瘀热互结的一类疾病,如子宫内膜异位症等,疗效良好,值得临床推广应用。     

Brood pouch-mediated polystyrene nanoparticle uptake during Daphnia magna embryogenesis

Nanoplastic debris is currently expected to be ubiquitously distributed in aquatic environments and an emerging environmental issue affecting organisms across trophic levels. While ingestion of particles receives most attention, other routes of uptake and cellular accumulation remain unexplored. Here, the planktonic filter feeder Daphnia magna was used to track routes of uptake and target tissues of polystyrene nanoparticles (PSNPs). A sublethal concentration of 5?mg L^?1 fluorescent PSNPs (25?nm) was used to monitor accumulation in adult animals as well as their embryos in the open brood pouch. A time series throughout embryonic development within the brood pouch revealed accumulation of PSNP in or on lipophilic cells in the early stages of embryonic development while the embryo is still surrounded by a chorion and before the beginning of organogenesis. In contrast, PSNP particles were neither detected in the gut epithelium nor in lipid droplets in adults. An ex vivo exposure of embryos to PSNP demonstrated a similar accumulation of PSNP in or on lipophilic cells, illustrating the likelihood of brood pouch-mediated PSNP uptake by embryos. By demonstrating embryo PSNP uptake via the brood pouch, data presented here give novel insights in bioaccumulation of nanoparticles and likely other lipophilic contaminants. Since this uptake route can occur within a diverse array of aquatic organisms, this study warrants consideration of brood pouch-mediated accumulation in efforts studying the hazards and risks of nanoparticle contamination.     

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.     

Hierarchical polymer coating for optimizing the antifouling and bactericidal efficacies

The bacteria-repellent and bactericidal functionalities in a single system are generally need to be carefully optimized in order to obtain the highest antibacterial performance. In this study, the controlled SI-PIMP strategy was developed for creating hierarchical polymer brushes possessing the bacteria-repellent and bactericidal functionalities. To obtain a bactericidal surface with minimal interference to its nonfouling property, optimization studies were conducted by facilely tailoring the surface density of the quaternary ammonium compound moieties through control over the monomer concentration. An optimal hierarchical polymer coating showed potent protein and bacteria repellence as well as certain bactericidal property. The longlasting antibacterial performance was also achieved due to the good balance between the dual functionalities. The tenability of the hierarchical polymer coating is applicable to surface chemistries for biosensors, molecular imaging, and biomedical applications.     

Effect of mu and kappa opioids on injury-induced microglial accumulation in leech CNS: involvement of the nitric oxide pathway

Damage to the leech or mammalian CNS increases nitric oxide (NO) production and causes accumulation of phagocytic microglial cells at the injury site. Opioids have been postulated to modulate various parameters of the immune response. Morphine and leech morphine-like substance are shown to release NO and suppress microglial activation. Regarding the known immuno-modulatory effects of selective mu and kappa ligands, we have assessed the effect of these agents on accumulation of microglia at the site of injury in leech CNS. Leech nerve cords were dissected, crushed with fine forceps and maintained in different concentrations of opiates in culture medium for 3 h and then fixed and double stained with Hoechst 33258 and monoclonal antibody to endothelial nitric oxide synthase (NOS). Morphine and naloxone (> or =10(-3) M) but not selective mu agonist, DAMGO [d-Ala2, N-Me-Phe-Gly5(ol)-enkephalin] and antagonist, CTAP [D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2] inhibited the microglial accumulation. The effect of morphine was abrogated by pre-treatment with naloxone and also non-selective NOS inhibitor, l-NAME [N(omega)-nitro-l-arginine-methyl-ester; 10(-3) M] implying an NO-dependent and mu-mediated mechanism. These results are similar to properties of recently found mu-3 receptor in leech, which is sensitive to alkaloids but not peptides. Both selective kappa agonist, U50,488 [3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl)cyclohexyl)-benzeneacetamide; > or =10(-3) M], and antagonist, nor-binaltorphimine (nor-BNI; > or =10(-3) M), inhibited the accumulation. The effect of nor-BNI was reversed by l-NAME. Immunohistochemistry showed decreased endothelial NOS expression in naloxone and U50,488-treated cords. Since, NO production at the injury site is hypothesized to act as a stop signal for microglias, opioid agents may exert their effect via changing of NO gradient along the cord resulting in disruption of accumulation. These results suggest an immuno-modulatory role for mu and kappa opioid receptors on injury-induced microglial accumulation which may be mediated via NO.