A highly tumor-targeted nanoparticle of podophyllotoxin penetrated tumor core and regressed multidrug resistant tumors

Podophyllotoxin (PPT) exhibited significant activity against P-glycoprotein mediated multidrug resistant (MDR) tumor cell lines; however, due to its poor solubility and high toxicity, PPT cannot be dosed systemically, preventing its clinical use for MDR cancer. We developed a nanoparticle dosage form of PPT by covalently conjugating PPT and polyethylene glycol (PEG) with acetylated carboxymethyl cellulose (CMC-Ac) using one-pot esterification chemistry. The polymer conjugates self-assembled into nanoparticles (NPs) of variable sizes (20–120 nm) depending on the PPT-to-PEG molar ratio (2–20). The conjugate with a low PPT/PEG molar ratio of 2 yielded NPs with a mean diameter of 20 nm and released PPT at ∼5%/day in serum, while conjugates with increased PPT/PEG ratios (5 and 20) produced bigger particles (30 nm and 120 nm respectively) that displayed slower drug release (∼2.5%/day and ∼1%/day respectively). The 20 nm particles exhibited 2- to 5-fold enhanced cell killing potency and 5- to 20-fold increased tumor delivery compared to the larger NPs. The biodistribution of the 20 nm PPT-NPs was highly selective to the tumor with 8-fold higher accumulation than all other examined tissues, while the larger PPT-NPs (30 and 120 nm) exhibited increased liver uptake. Within the tumor, >90% of the 20 nm PPT-NPs penetrated to the hypovascular core, while the larger particles were largely restricted in the hypervascular periphery. The 20 nm PPT-NPs displayed significantly improved efficacy against MDR tumors in mice compared to the larger PPT-NPs, native PPT and the standard taxane chemotherapies, with minimal toxicity.     

表观遗传调控与青光眼发病机制研究进展

表观遗传学主要机制包括DNA甲基化、组蛋白修饰和miRNAs等。这些机制将环境与基因相联系，在基因的特异性表达过程中发挥重要作用，影响疾病的表型。青光眼是全球第一大不可逆致盲眼病，其发病机制复杂，受遗传和环境的共同影响。本文分别对DNA甲基化、组蛋白修饰和miRNAs参与青光眼发病的机制进行综述，以期为临床诊治提供参考。     

A novel surgical technique to prevent post-enucleation conjunctival cyst:conjunctival staining with methylthioninium

Dear Editor,Conjunctival cyst of the orbit acquired from enucleation is an infrequent but serious complication;which can occur in 3%-7%of patients,more commonly after a secondary procedure;.The most common manifestations are the inability to retain the external prosthesis.     

Efficacy of lianhuaqingwen granules in the management of chronic rhinosinusitis without nasal polyps

ObjectivesChronic rhinosinusitis (CRS) is a complicated disease with clinical symptoms that are impacted by the absence or presence of nasal polyps (CRSsNP or CRSwNP). Understanding of the different treatments of CRS is very significant in selecting appropriate therapies and preventing exacerbation relevant to this chronic inflammation. This study was aimed to evaluate the effect of Chinese traditional medicine lianhuaqingwen granules on CRSsNP.Materials and methodsCRSsNP patients were enrolled and randomized into placebo or lianhuaqingwen (LHQW) granules treatment group (placebo or LHQW group). Their clinical symptoms were scored using Visual Analog Scale (VAS) and Sino-Nasal Outcome Test (SNOT)-22. Nitric oxide (NO) from nasal cavity and sinus and nasal resistance were also examined. Then, nasal biopsy samples and nasal lavage fluid (NLF) were obtained from these patients, and histologic characteristics of nasal mucosa and T cell subpopulations patterns in the NLF were evaluated. Finally, inflammatory mediators in the NLF were assessed in both groups.ResultsOne hundred and forty patients with CRSsNP finished this one-month study. VAS and SNOT-22 scores and nasal resistance were all decreased distinctly after the treatment of LHQW, but not after placebo. However, the nasal NO concentration was increased in LHQW administration group in comparison with placebo group. There were significant differences in above parameters between these two treatments. Histologic changes in nasal mucosa were improved only in LHQW group. CD4⁺ and CD8⁺ T cells were all downregulated in the LHQW treatment group, but not in placebo group. Inflammatory mediators from the NLF were decreased in LHQW treatment group compared to placebo group. Furthermore, there were significant changes between these two groups in CD4⁺ and CD8⁺ T cell subpopulations and concentrations of inflammatory substances.ConclusionThese findings demonstrate that LHQW granules treatment may control the inflammation in nasal mucosa and result in the improvement of CRSsNP. This Chinese medicine might become a promising therapy in the management of this disease.     

免水分离超声乳化白内障摘除术临床观察

目的 :探讨免水分离术在超声乳化白内障摘除术中临床应用的有效性。方法 :随机选择白内障患者 2 0 0只眼 ,分两组。一组 (对照组 ) 95例 10 0只眼进行常规水分离术 ,二组 (观察组 ) 94例 10 0只眼 ,行免水分离术 ,所有患者均由同一医师进行超声乳化白内障摘除术联合人工晶体植入。临床观察超声乳化能量和时间 ,术后第一天、第三天、一周时视力 ,术中、术后并发症。结果 :( 1)平均超声能量Ⅰ、Ⅱ、Ⅲ、Ⅳ级核 ,一组分别是 :( 10 5 6± 4 16) %、 ( 17 88± 2 2 6) %、 ( 2 9 2 2± 3 5 4) %、 ( 3 7 88± 2 67) % ;二组分别是 ( 11 3 0± 1 89) %、 ( 18 76± 1 61) %、 ( 2 7 99± 3 5 8) %、 ( 3 9 2 2± 3 3 3 ) % ;两组平均超声能量差异无显著意义 (t =-0 5 12、 -1 496、 1 70 6、 -1 3 60 ,P =0 615、 0 14 2、 0 0 91、 0 182 ) ;平均超声时间一组分别为 ( 7 5 6±3 2 1)s、 ( 2 6 68± 5 15 )s、 ( 71 72± 17 2 2 )s、 ( 13 7 71± 3 8 60 )s ,二组分别为 ( 9 10± 1 2 0 )s、 ( 2 4 71± 4 0 9)s、 ( 76 17± 18 74)s、 ( 12 2 0 9± 3 5 14 )s ,两组平均超声时间差异无显著意义 (t =-1 42、 -1 415、 -1 3 69、 1 3 3 3 ,P =0 173、0 164、 0 174、 0 190 )。 ( 2 )术后一     

鼓室成形术中电钻及吸引噪声的安全性评估

目的 :探讨耳显微外科手术中电钻及吸引的噪声 ,对术耳和非术耳的耳蜗功能所产生的影响。方法 :采用ND10型声级计 ,对鼓室成形术中不同规格和不同种类的钻头及吸引所产生的噪声进行检测 ,并分别比较术耳术前和术后 1个月的纯音骨导阈值以及非术耳术前和术后 1个月的骨导阈值。结果 :术中电钻钻头与吸引所致噪声强度分别为 82～ 10 6dB(A)和 71～ 84dB(A) ,术前与术后 1个月左右双耳纯音骨导阈值变化差异无统计学意义 (P >0 .0 5 )。结论 :鼓室成形术中电钻及吸引器的使用是安全的 ,对双侧耳蜗功能无明显不良影响     

玻璃体切除联合不同手术方式治疗晶状体脱位于玻璃体腔的疗效观察

目的探讨玻璃体切除联合不同手术方式治疗晶状体脱位于玻璃体腔的临床疗效。方法眼外伤、白内障手术中并发症和马凡综合征及不明原因所造成的晶状体脱位于玻璃体腔的患者27例(29只眼),采用玻璃体切除联合不同的手术方式取出晶状体,包括标准睫状体扁平部三通道闭合式玻璃体切除联合晶状体切除术、玻璃体切除联合晶状体超声粉碎术、玻璃体切除联合应用全氟化碳液体角膜缘切口取出晶状体术等。结果29只眼脱位于玻璃体腔之晶状体均被成功地取出,视力均有不同程度的提高。8只眼矫正视力恢复至≥0.3,7只眼继发性青光眼,手术后除1只眼需局部用降眼压药外,眼压均得到控制;6只眼伴有视网膜脱离者,联合视网膜复位手术,使其复位成功;10只眼同期行人工晶状体睫状沟缝线固定。29只眼无1例发生严重并发症。结论脱位于玻璃体腔之晶状体如果长期存留将会产生多种较为严重的并发症,因此,在高眼压和炎症反应得到基本控制的前提下,根据不同情况,应用玻璃切除手术联合不同的手术方式,尽早及时地取出脱位于玻璃体腔之晶状体,对视功能的恢复和减少并发症的发生有着重要的临床治疗价值。     

Identification of promotion and prevention associated surgeon behaviors in the operating room to facilitate resident self-regulated learning

BackgroundThe regulatory focus theory (RFT) posits that people can pursue goals with a promotion or prevention focus. Greater alignment of RFT motivational styles between faculty and residents may enhance resident operative autonomy. This study establishes a set of faculty behaviors residents can identify to infer faculty motivational styles.Methods10 behaviors associated with promotion and prevention motivational styles were identified. General surgery residents rated faculty on how strongly they exhibit these behaviors. Faculty conducted a self-assessment of how strongly they exhibit these behaviors.ResultsThere is a positive correlation between resident and faculty ratings for the promotion-associated behaviors of “works quickly,” “high energy,” and “mostly provides broad oversight,” and for the prevention-associated behaviors of “works slowly and deliberately,” “quiet and calm,” and “preference for vigilant strategies.”ConclusionResidents can observe faculty operative behaviors to infer faculty motivational styles. Residents may use this knowledge to adjust to faculty motivational styles and enhance operative interactions.     

增生性玻璃体视网膜病变玻璃体切割物的细胞凋亡观察

目的观察增生性玻璃体视网膜病变玻璃体切割物的细胞凋亡情况 。方法收集60例不同分级的增生性玻璃体视网膜病变患者的玻璃体切割物,核苷酸末端转移酶介导dUTP缺口翻译法(TdT-mediated dUTP nick end label ling method,TUNEL法)标记凋亡细胞,光镜观察。结果60例患者的玻璃体切割物均有细胞凋亡的特征性改变,随着病变程度的加重,非色素细胞凋亡总数逐渐减少,并出现色素细胞凋亡。结论增生性玻璃体视网膜病变存在不同类型细胞的凋亡,细胞凋亡是调控其病变程度的重要机制之一。(中华眼底病杂志,1999,15:81-83)