中医药分期防治新型冠状病毒肺炎的药性功效分析

新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)疫情严峻复杂,探讨中医药防治COVID-19处方的用药规律及特点具有重要意义。该研究收集2020年1月1日至2月18日国家卫生健康委员会,7个省市卫生健康委员会、国家中医管理局发布的和《新型冠状病毒肺炎中医诊疗手册》收录的中医药防治COVID-19诊疗方案以及3位国医大师、4位知名中医药专家所拟的方药,按照纳入、排除标准进行筛选,应用EpiData 3.0软件,建立"防治新型冠状病毒肺炎中医处方库""防治新型冠状病毒肺炎常用中药库",共收集有效中药处方93首,组成药物共计157味。应用SPSS 18.0软件进行数据分析,结果发现:①药性寒、温居多,其中性寒69味,占43.95%;性温57味,占36.31%;性热较少,仅占1.27%;②味苦、辛、甘药物较多,不同时期药味有异,初期以辛味居多,中期、重症期以苦味为主,恢复期多用甘味药;③归经以入肺、胃、心者多,入肺经最多,占24.55%;初、中期多入肺胃,重症期则入心肾;④口服药物多无毒,仅6味药物具有毒性,分别是苦杏仁、绵马贯众、重楼、细辛、半夏、炮附片;⑤以具有解表、化湿、清热、补虚、化痰止咳平喘5类功效的药物居多,初期解表与清热并重,各占18.81%;中期化痰止咳平喘药物使用多,占29.61%;重症期清热使用最多,占33.33%;恢复期补虚使用最多,占36.47%。中药防治COVID-19的药性特点和功效分布与中医对其病因、病位、病机的认识紧密相关,临证辨治尤需注重分期用药及因地制宜。     

色谱指纹图谱技术和化学计量学方法分析药对生姜-白术挥发油成分

目的对由生姜、白术及其药对中提取的挥发油组分进行检测。方法采用的方法是气相色谱-质谱指纹图谱技术(GC-MS)和交互移动窗口因子法(AMWFA)。定性分析的方法是质谱库和程序升温保留指数结合,而定量分析是采取总体积积分法。结果生姜、白术和药对生姜-白术的挥发油分别定性59、40和45个成分,占总含量的91.48%、93.52%和89.73%,药对生姜-白术与生姜、白术的共有组分分别为25和12个。结论药对挥发油的组分并不是两种单味药的简单加和。     

ICL植入术矫正超高度近视的临床效果观察

目的:评估有晶状体眼后房型人工晶状体(ICL)矫正超高度近视的疗效及安全性。方法:对超高度近视患者20例40眼接受普通型ICL或散光型后房型人工晶状体(TICL)治疗,术前屈光度球镜-10.0～-18.0D,柱镜-0.25～-3.00D,等效球镜-15.32D,术后随访12mo,观察指标包括UCVA,BCVA、角膜地形图、主观和客观验光、角膜内皮细胞计数、眼压测量、裂隙灯检查。结果:术后12mo,裸眼视力≥0.8者占80.0%(32眼)。30.0%(12眼)的术眼BCVA较术前提高1行,15.0%(6眼)的术眼BCVA较术前提高2行。术后12mo术眼屈光度在±0.50D者达70.0%(28眼)。术前患者平均眼压为16±2.8mmHg,术后6mo平均眼压为17±3.4mmHg,术前术后相比较差异无显著性(t=0.518,P=0.776),术前患者角膜内皮细胞计数平均为2823±243.6个/mm2,术后6mo平均为2709±273.2个/mm2,术前术后比较无显著性差异(t=0.794,P=0.422)。未发生继发性青光眼、视网膜脱离及并发性白内障。结论:ICL植入术矫正超高度近视具有良好的疗效和安全性,远期效果有待进一步观察。     

卵巢高反应患者全胚冷冻临床应用研究

目的 探讨卵巢高反应患者新鲜移植周期与冻融胚胎移植(frozen-thawed embryo transfer, FET)周期妊娠结局的差异,了解促排卵药物对新鲜周期子宫内膜容受性的影响。方法 回顾性分析2011年1月至2013年12月在中国医科大学附属盛京医院生殖中心促排卵周期行新鲜胚胎移植(582例)和全部胚胎冷冻再行FET(167例)周期的临床妊娠率、生化妊娠率、种植率、胚胎停育率、异位妊娠率、流产率、持续妊娠率和多胎妊娠率。结果 582例促排卵周期新鲜胚胎移植与167例FET周期比较临床妊娠率（42.44% vs. 69.46%）,生化妊娠率（7.22% vs. 2.99%）,种植率（28.27% vs. 48.99%）,胚胎停育率（8.10% vs. 7.76%）,异位妊娠率（5.26% vs. 4.31%）,流产率（8.10% vs. 6.90%）,持续妊娠率（34.19% vs. 59.88%）,多胎率（35.22% vs. 37.93%）。组间比较临床妊娠率、生化妊娠率、种植率、持续妊娠率差异均有统计学意义(P<0.05)。结论 全胚冷冻再行冻融周期移植可显著提高卵巢高反应患者临床妊娠率、种植率及持续妊娠率,不增加多胎率的发生,可获得更为理想的妊娠结局。新鲜周期高雌激素可能对子宫内膜容受性有损害作用。     

Elucidating the mechanism of nucleation inhibition of pathology crystallization of gout based on the evidence from amorphous form and in solution

The first gout attack in a hyperuricaemic patient may be regarded as a nucleation event which is caused by monosodium urate monohydrate (MSUM) deposition in the synovial fluid. The effect of Tailor-Made Inhibition (TMI) may be effective as drugs for the prevention of aberrant nucleation and crystallization. Therefore, the understanding of the underlying mechanisms in inhibiting the MSUM nucleation by TMI has proven to be of great significance. Yet most of the published studies about nucleation inhibition have tended to focus on simpler molecular models with a hydrogen-bonded acceptor and donor, which may be not suitable for the uric acid molecule with multiple hydrogen-bonded acceptors and donors under physiological conditions. Herein, the mechanisms of nucleation inhibition of MSUM were explored in a simulated biological environment (0.15 M Na⁺ and pH 7.40) in the presence and absence of TMI. And the evidence of nucleation inhibition by TMI in solution and the amorphous form of MSUM was investigated by HNMR, IR, Raman, PXRD, Dynamic light scattering (DLS), induction time measurements, and density functional theory (DFT) calculations. Results showed that the inhibition comes from a combination of kinetic and thermodynamic effects, with an impact of kinetics as the TMI inhibition effects far exceeded what could be accounted for by changes in usual factors of classical nucleation theory. The data demonstrated that the complex between urate and TMI disturbed the formation of two-dimensional sheets of sodion and purine rings parallel to the (011) plane and further impeded the formation of a three-dimensional structure with aromatic stacking interactions in solution. To our knowledge, the nucleation inhibition of TMI is achieved by suppressing interplanar stacking, which is a mechanism proposed for the first time.

Xanthine, a tailor-made inhibitor, could suppress nucleation in the crystallization of gout pathology by blocking the dominant interplanar accumulation in a solution.     

SMILE术后1个月患者瞳孔中心和角膜顶点实际角膜基质透镜厚度与预计厚度的差异

目的　探讨飞秒激光小切口角膜基质透镜取出术（SMILE）术后1个月患者瞳孔中心和角膜顶点实际角膜基质透镜厚度与预计厚度的差异。方法　选取2021年1月至4月在西安高新医院眼科屈光门诊行SMILE的患者66例（132眼）作为研究对象。分别于术前和术后1个月应用眼前节三维成像分析系统Pentacam测量患者瞳孔中心角膜厚度和角膜顶点厚度,检测患者视力及等效球镜度。将术前Pentacam检查结果作为“A图”,术后1个月检查结果作为“B图”,（A图－B图）数据即可得出每个坐标的角膜厚度差值,角膜厚度差值中瞳孔中心的差值(ΔCT_p)和角膜顶点的差值(ΔCT_v)即为实际角膜基质透镜厚度。角膜基质透镜厚度误差（E）=预计角膜基质透镜厚度-实际角膜基质透镜厚度,其中预计角膜基质透镜厚度为VisuMax飞秒激光手术设计软件预计的角膜厚度（LT）,瞳孔中心角膜基质透镜厚度误差E_p=LT_p-ΔCT_p;角膜顶点角膜基质透镜厚度误差E_v=LT_v-ΔCT_v。分析实际角膜基质透镜厚度与预计厚度的关系。结果　术后1个月所有患者均无角膜水肿及炎症反应发生,眼压正常;132眼患者裸眼视力均达到或超过术前最佳矫正视力。术后1个月132眼患者等效球镜度范围为-0.50 ~+0.50 D。患者ΔCT_p为43~133（86.83±16.81）μm,明显低于LT_p［55~130（96.89±15.92）μm］,差异有统计学意义（t=-17.71,P<0.01）。患者ΔCT_v为43~131（86.95±16.66）μm,明显低于LT_v［55~130（96.89±15.92）μm］,差异有统计学意义（t=-17.65,P<0.01）。患者E_p为-7~28（10.07±6.53）μm,E_v为-7~27（9.95±6.48）μm。实际角膜基质透镜厚度随着预计厚度的增加而增加。LT_p每增加1 μm,ΔCT_p增加0.97 μm ［y=-7.5+0.97x（R²=0.85,P<0.01）,x为LT_p,y为ΔCT_p］; LT_v每增加1 μm,ΔCT_v增加0.96 μm［y=-6.54+0.96x（R²=0.85,P<0.01）,x为LT_v,y为ΔCT_v］。结论　SMILE手术实际制作的角膜基质透镜厚度明显低于预计厚度,实际厚度与预计厚度呈线性关系;角膜顶点位置的检测结果与VisuMax手术设计软件所预计的角膜基质透镜厚度更接近。     

Dihydroartemisinin is an inhibitor of ovarian cancer cell growth

Aim： To investigate the anticancer activity of dihydroartemisinin （DHA）, a derivative of antimalaria drug artemisinin in a panel of human ovarian cancer cell lines. Methods： Cell growth was determined by the MTT viability assay. Apoptosis and cell cycle progression were evaluated by a DNA fragmentation gel electro-phoresis, flow cytometry assay, and TUNEL assay; protein and mRNA expression were analyzed by Western blotting and RT-PCR assay. Results： Artemisinin and its derivatives, including artesunate, arteether, artemether, arteannuin, and DHA, exhibit anticancer growth activities in human ovarian cancer cells. Among them, DHA is the most effective in inhibiting cell growth. Ovarian cancer cell lines are more sensitive （5-10-fold） to DHA treatment compared to normal ovarian cell lines. DHA at micromolar dose levels exhibits a dose- and time-dependent cytotoxicity in ovarian cancer cell lines. Furthermore, DHA induced apoptosis and G2 cell cycle arrest, accompanied by a decrease of Bcl-XL and Bcl-2 and an increase of Bax and Bad. Conclusion： The promising results show for the first time that DHA inhibits the growth of human ovarian cancer cells. The selective inhibition of ovarian cancer cell growth, apoptosis induction, and G2 arrest provide in vitro evidence for further studies of DHA as a possible anticancer drug in the clinical treatment of ovarian cancer.     

Cocktail探针药物法评价糖尿病大鼠体内细胞色素P450不同亚型的活性

目的:探讨链脲佐菌素(STZ)诱导糖尿病模型大鼠体内细胞色素P450酶(CYPs)6种亚型活性及蛋白含量的变化,为临床合理用药提供参考.方法:将大鼠随机分为空白对照组、糖尿病1周组、4周组和8周组.应用"Cocktail"探针药物法评价各组大鼠血浆中各探针药物的浓度,比较空白对照组和3组糖尿病模型组各探针药物的药动学参数,评价糖尿病大鼠体内细胞色素P450酶亚型1A2、2D6、2C19、2C9、2E1和3A4活性的变化;选择酶联免疫吸附测定法(ELISA)检测糖尿病大鼠肝脏中此6种CYPs亚型酶蛋白相对表达量的变化.结果:相比于空白组,糖尿病4周和8周组大鼠体内咖啡因AUC分别降低了62.78%和79.31%(P<0.01),校正后的清除率(CL Z)分别升高了5.12和52.35倍(P<0.05,P<0.01);糖尿病模型组大鼠体内美托洛尔AUC、t 1/2z和CL Z均无显著变化;糖尿病8周大鼠体内氯唑沙宗AUC降低了60.58%(P<0.01),CL Z升高了1.2倍(P<0.01);糖尿病4周和8周组大鼠体内奥美拉唑AUC降低了55.60%和81.42%(P<0.05,P<0.01),CL Z升高了27.50和41.25倍(P<0.01);8周大鼠甲苯磺丁脲AUC降低了45.39%(P<0.05)、CL Z升高了83.33%(P<0.01);糖尿病1周和8周组大鼠体内咪达唑仑AUC降低了43.23%和53.87%(P<0.05,P<0.01),CL Z升高了1.33和2.04倍(P<0.05).相比于空白组,糖尿病1周和4周组大鼠肝脏中CYP1A2蛋白相对表达量升高了24.60%和26.41%(P<0.05),糖尿病1周组大鼠CYP3A4蛋白相对表达量降低了24.62%(P<0.05),CYP2D6、2E1、2C19和2C9蛋白相对表达量无变化.结论:与空白组相比,糖尿病模型组大鼠体内CYP1A2、2E1、2C19、2C9和3A4活性均被诱导,而CYP2D6活性未发生变化;与空白组相比,糖尿病1周、4周组的大鼠肝脏中CYP1A2蛋白相对表达量明显升高,糖尿病1周组大鼠肝脏中CYP3A4蛋白相对表达量明显降低,CYP2D6、2E1、2C9和2C19亚型酶蛋白相对表达量均未发生显著变化.     

薄层扫描色谱法测定洗剂中苯甲酸苄酯与邻苯二甲酸二丁酯的含量

采用双波长薄层色谱扫描法同时测定复方苯甲酸苄酯洗剂中苯甲酸苄酯与邻苯二甲酸二丁酯的含量，点样后能将本品中两个有效成分很好地分离，在ＧＦ２５４板上，经甲苯∶二氯甲烷（２∶１）混合溶剂展开，反射锯齿扫描测定，λｓ２３５ｎｍ，λＲ２６０ｎｍ，以外标两点法定量。苯甲酸苄酯与苯二甲酸二丁酯测定的线性范围分别为６．０～３０．０μｇ和１０．０～５０．０μｇ。方法可行，结果满意。     

Mesoporous silica-coated gold nanostars with drug payload for combined chemo-photothermal cancer therapy

Abstract

Combined chemo-photothermal therapy is attracting increasing attention in the treatment of cancers. In this work, PEGylated mesoporous SiO₂-coated gold nanostars (GNS@mSiO₂-PEG) were synthesised without using the cytotoxic surfactant cetyltrimethylammonium bromide as the template. Mesoporous nanostructures were obtained by poly(vinylpyrrolidone) protection of the outer silica shell and NaOH etching of the inner shell. GNS@mSiO₂-PEG exhibited good dispersity in medium and excellent photothermal effects. Loading capacity for the anticancer drug doxorubicin (DOX) was ～17.9%, and the drug release profile was pH- and light-responsive. In vitro studies revealed that the as-prepared nanocomposites featured good biocompatibility. Furthermore, the nanocomposites were readily internalised by cancer cells, and a combined chemo-photothermal therapy assay revealed that DOX-loaded GNS@mSiO₂-PEG have a higher therapeutic efficiency than individual therapies, demonstrating suitable synergistic effects.