低氧环境下Notch信号通路对人牙髓干细胞成牙本质向分化的影响

目的探讨低氧环境下通过低氧诱导因子-1α（HIF-1α）调控Notch信号通路对人牙髓干细胞（HDPSC）成牙本质向分化能力的影响。 方法组织块酶消化法培养HDPSC,给予氯化钴（CoCl₂）诱导的化学性低氧环境,Western blot检测HIF-1α蛋白表达,茜素红染色检测细胞矿化结节形成能力,反转录聚合酶链反应（RT-PCR）检测Notch下游靶基因Hes1与成牙本质相关基因的表达;进一步加入Notch信号通路特异性阻断剂γ分泌酶抑制剂（GSI）,观察以上指标的变化。报告基因方法检测HIF-1α对Notch信号通路的调控作用。采用R version 3.5.3软件进行统计分析,计量资料进行正态检验,多组间比较采用单因素方差分析（方差齐）或Kruskal-Wallis H检验（方差不齐）,两两比较采用LSD-t检验（方差齐）或Mann-Whitney U检验（方差不齐）。 结果（1）CoCl₂诱导的低氧条件下HDPSC中的HIF-1α蛋白水平上调,Notch下游靶基因Hes1 mRNA相对表达量为1.46 ± 0.12,相比常氧组（1.06 ± 0.09）显著增高（t = -4.64,P = 0.012）;GSI处理阻断Notch信号通路后,低氧条件下HDPSC中HIF-1α蛋白水平下调,Hes1 mRNA相对表达量降低至0.82 ± 0.14,与处理前相比差异有统计学意义（t = 5.98,P = 0.004）;常氧条件下GSI处理后的HDPSC中HIF-1α蛋白水平也明显下调,Hes1 mRNA相对表达量（0.30 ± 0.09）相比处理前也显著降低（t = 10.08,P = 0.001）;（2）矿化诱导后的茜素红染色结果显示：低氧处理后,HDPSC细胞成牙本质分化能力下降;GSI处理后,成牙本质向分化能力增强。成骨/牙本质相关基因mRNA表达水平检测结果显示：低氧处理后,BSP、OCN和DSPP的mRNA相对表达量分别为0.53 ± 0.14、0.43 ± 0.20、0.48 ± 0.11,相比常氧组（1.21 ± 0.12、1.08 ± 0.19、1.03 ± 0.13）显著降低（t_BSP = 6.30,P_BSP = 0.003;t_OCN = 4.07,P_OCN = 0.015;t_DSPP = 5.67,P_DSPP = 0.005）;GSI处理后,低氧条件下BSP、OCN和DSPP mRNA相对表达量分别为0.99 ± 0.13、1.09 ± 0.13、0.95 ± 0.16,与处理前相比显著增高（t_BSP = -4.17,P_BSP = 0.014;t_OCN = -4.83,P_OCN = 0.012;t_DSPP = -4.30,P_DSPP = 0.017）,常氧条件下BSP、OCN和DSPP mRNA相对表达量分别为1.73 ± 0.20、1.55 ± 0.08、1.52 ± 0.14,与处理前相比显著增高（t_BSP = -3.84,P_BSP = 0.027;t_OCN = -3.99,P_OCN = 0.035;t_DSPP = -4.43,P_DSPP = 0.011）。（3）荧光素酶报告基因结果显示,HIF-1α可调控NICD启动子,使双荧光素酶相对表达活性为5.37 ± 0.12,与对照组（2.09 ± 0.15）相比显著增强（t = -28.92,P<0.001）,提示HIF-1α可能使Notch信号通路激活。 结论低氧引起HDPSC中HIF-1α升高并可能通过激活Notch信号通路抑制其成牙本质向分化能力。     

内镜下分段切除儿童巨大肠息肉的临床疗效探讨

目的该文旨在探讨内镜下分段切除儿童巨大肠息肉的临床疗效及安全性。方法回顾性分析该院消化内科和普外科收治的66例巨大肠息肉患儿,43例采取内镜下分段切除治疗,23例行外科手术。观察两组患儿禁食时间、住院时间及不良反应发生情况。结果两组患儿均成功进行息肉切除术,内镜治疗组在禁食时间、住院时间及住院费用上均优于外科手术组(P 0.05),两组患儿不良反应发生情况无明显差异。结论内镜下分段切除儿童巨大肠息肉疗效满意,操作安全、创伤小,值得临床推广。     

Unilateral facial injection of Botulinum neurotoxin A attenuates bilateral trigeminal neuropathic pain and anxiety-like behaviors through inhibition of TLR2-mediated neuroinflammation in mice

ObjectivesIn this study, we investigated the possible analgesic effects of Botulinum toxin type A (BoNT/A) on trigeminal neuralgia (TN). A modified TN mouse model was established by chronic constriction injury of the distal infraorbital nerve (dIoN-CCI) in mice, and the possible roles of microglia toll-like receptor 2 (TLR2) and neuroinflammation was investigated.MethodsMale C57BL/6 mice were divided into 3 groups, including sham group, vehicle-treated TN group and BoNT/A-treated TN group. Bilateral mechanical pain hypersensitivity, anxiety-like and depressive-like behaviors were evaluated by using von Frey test, open field, elevated plus-maze testing, and forced swimming test in mice, respectively. The mRNA or protein expression levels of toll-like receptors (TLRs), glia activation markers and proinflammatory factors in the trigeminal nucleus caudalis (TNC) were tested by RT-qPCR, immunofluorescence and Western blotting. We also tested the pain behaviors of TN in Tlr2^−/− mice.ResultsWe found that unilateral subcutaneous injection of BoNT/A into the whisker pad on the ipsilateral side of dIoN-CCI mice significantly attenuated bilateral mechanical pain hypersensitivity and anxiety-like behaviors induced by dIoN-CCI surgery in mice. The dIoN-CCI surgery significantly up-regulated the expression of TLR2, MyD88, CD11b (a microglia marker), IL-1β, TNF-α and IL-6 in the ipsilateral TNC in mice, and BoNT/A injection significantly inhibited the expression of these factors. Immunostaining results confirmed that BoNT/A injection significantly inhibited the microglia activation in the ipsilateral TNC in dIoN-CCI mice. TLR2 deficiency also alleviated bilateral mechanical pain hypersensitivity and the up-regulation of MyD88 expression in the TNC of dIoN-CCI mice.ConclusionThese results indicate that unilateral injection of BoNT/A attenuated bilateral mechanical pain hypersensitivity and anxiety-like behaviors in dIoN-CCI mice, and the analgesic effects of BoNT/A may be associated with the inhibition of TLR2-mediated neuroinflammation in the TNC.     

Recent advances in liquid hydrosilane-mediated catalytic N-formylation of amines with CO2

Carbon dioxide is an ideal raw material for the synthesis of complex organic compounds because of its rich, non-toxic, and good physical properties. It is of great significance to transform CO₂ into valuable fine chemicals and develop a green sustainable cycle of carbon surplus. Based on hydrosilane as a reducing agent, this work summarizes the recent applications of reductive amidation of CO₂ using different catalysts such as organocatalysts, ionic liquids (ILs), salts, transition metal complexes, and solvents. The main factors affecting the reductive amidation of CO₂ and the possible reaction mechanism are discussed. Moreover, the future orientation and catalytic systems of the formylation of amines with CO₂ and hydrosilane are prospected.

This review depicts different types of catalyst systems developed for upgrading of amines and carbon dioxide into N-formylated products in the presence of hydrosilane, with attention on reaction mechanism and process optimization.     

COVID-19疫情下慢病患儿的药学服务模式

2019年12月我国发生新型冠状病毒感染,儿童、婴幼儿甚至新生儿均有感染病例。此疫情下,如何开展高质量的儿科药学服务、保障患儿安全用药,是目前儿科药师的重点工作。因此,本文基于疫情期间儿童慢病用药特点与特殊需求,结合长期慢病患儿的药学服务经验和疫情期间的实际工作,从慢病患儿新型冠状病毒感染用药资料库的构建、线上线下相结合药学服务的开展、分级药学服务策略的探索等方面归纳相关药学服务模式,以期为特殊时期儿童慢病服务开展提供参考。     

酒石酸布托啡诺、地佐辛与盐酸托烷司琼在镇痛泵内配伍的稳定性考察

目的:考察酒石酸布托啡诺、地佐辛、盐酸托烷司琼在0.9%氯化钠注射液中的配伍稳定性。方法:模拟临床实际用药的配伍浓度和使用环境,检测0,1,4,6,24,48,72 h外观、pH、相对百分含量的变化。结果:酒石酸布托啡诺、地佐辛与盐酸托烷司琼的配伍液在72 h内pH未出现明显变化,外观稳定,各药品成分相对百分含量也没有明显变化。结论:在室温条件下,酒石酸布托啡诺、地佐辛与盐酸托烷司琼在0.9%氯化钠注射液中72 h内保持稳定。因此,酒石酸布托啡诺(6 mg)、地佐辛(20 mg)与盐酸托烷司琼(10 mg)可以配伍使用,在镇痛泵内配伍稳定。     

盐酸特比萘芬醇类脂泡囊凝胶离体和在体透皮特点研究

目的:研究盐酸特比萘芬醇类脂泡囊凝胶在体和离体透皮特点。方法:采用Franz扩散池进行体外透皮实验,考察盐酸特比萘芬醇类脂泡囊凝胶、脂质体凝胶和普通凝胶经皮渗透性和皮肤滞留量;以小鼠为实验动物,3种凝胶腹部经皮给药,考察盐酸特比萘芬的血药浓度和皮肤滞留量,对比不同类型凝胶剂的透皮效果。结果:离体透皮扩散实验中,透皮速率排序为:脂质体凝胶>醇类脂泡囊凝胶>普通凝胶;皮肤内24 h累积滞留量排序为:醇类脂泡囊凝胶>脂质体凝胶>普通凝胶。在体透皮吸收实验中,皮肤内6 h累积滞留量排序为:醇类脂泡囊凝胶>脂质体凝胶>普通凝胶。3种凝胶中的盐酸特比萘芬在皮肤深层中的滞留量均远远大于角质层,醇类脂泡囊凝胶中药物在皮肤深层的滞留量远大于另外两种凝胶,而脂质体凝胶和普通凝胶在皮肤深层的滞留量无明显差异。结论:醇类脂泡囊对盐酸特比萘芬透皮吸收具有一定的促进作用,同时也能显著提高盐酸特比萘芬在皮肤内特别是皮肤深层中的滞留量,为治疗深部皮肤真菌感染提供了一种新方法。     

儿童入托期间首次上呼吸道感染前后咽部菌群及其药敏变化

目的 探讨健康学龄前儿童入托期间发生AURI前后咽部菌群及其药敏结果变化,为抗生素合理使用提供理论依据。方法 119名健康学龄前儿童在入托前体检时、入托48h后首次发生AURI时采集咽拭子标本行细菌培养鉴定及药物敏感试验,分析发病前后咽部细菌构成比例及药物敏感性的变化。结果 91名儿童首次AURI发病后咽拭子培养分离2+及以上细菌菌株与入托前体检差别具有统计学意义(χ2=4.607,P=0.032)。发病前咽部定植菌主要有草绿色链球菌、黏膜炎莫拉菌、肺炎链球菌等,发病后新增乙型溶血性链球菌、大肠埃希菌、化脓性链球菌、光滑假丝酵母菌,仅乙型溶血性链球菌前后比例差别有统计学意义(χ2=7.280,P=0.014)。对半定量分析2+及以上的细菌行药敏试验后发现细菌对常见抗菌素不同程度耐药。分析数量前三位的草绿色链球菌、黏膜炎莫拉菌以及肺炎链球菌敏感结果,草绿色链球菌对头孢噻肟、黏膜炎莫拉菌对青霉素及头孢呋辛发病后药物敏感性较发病前下降具有统计学意义(P值分别为0.029、0.048、0.029),其余细菌前后药敏差异均无统计学意义。结论 儿童入托期间首次AURI后咽拭子培养细菌数量及种类较感染前明显增加,发病后细菌对常见抗生素耐药率加重,应重视规范抗生素的使用。     

香叶木素固体脂质纳米粒的制备及质量评价

目的 制备香叶木素固体脂质纳米粒并对其进行质量评价。方法 采用溶剂注入法制备香叶木素固体脂质纳米粒,用 Box-Benhnken效应面法优化处方,并通过包封率、微观形态、粒径分布和Zeta电位对香叶木素固体脂质纳米粒的质量进行评价。 结果 香叶木素固体脂质纳米粒最优处方组成：表面活性剂浓度3.39%,棕榈酸浓度0.116%,脂药质比为21:100,制备的香叶木素 固体脂质纳米粒外观澄清透明,带淡蓝色乳光;平均粒径为(91.73±3.18)nm(n=3),PDI为0.228,电位为(-11.46±0.74)mV(n=3);包 封率为95.13%,载药量为9.04%;透射电镜照片显示纳米粒大小均一,呈球形或类球形。 结论 该处方可用于香叶木素固体脂 质纳米粒的制备,工艺简单,稳定可行。