Near-Infrared Light-Sensitive Liposomes for the Enhanced Photothermal Tumor Treatment by the Combination with Chemotherapy

Purpose

To develop a near-infrared (NIR) light-sensitive liposome, which contains hollow gold nanospheres (HAuNS) and doxorubicin (DOX), and evaluate their potential utility for enhancing antitumor activity and controlling drug release.

Methods

The liposomes (DOX&HAuNS-TSL) were designed based on a thermal sensitive liposome (TSL) formulation, and hydrophobically modified HAuNS were attached onto the membrane of the liposomes. The behavior of DOX release from the liposomes was investigated by the dialysis, diffusion in agarose gel and cellular uptake of the drug. The biodistribution of DOX&HAuNS-TSL was assessed by i.v. injection in tumor-bearing nude mice. Antitumor efficacy was evaluated both histologically using excised tissue and intuitively by measuring the tumor size and weight.

Results

Rapid and repetitive DOX release from the liposomes (DOX&HAuNS-TSL), could be readily achieved upon NIR laser irradiation. The treatment of tumor cells with DOX&HAuNS-TSL followed by NIR laser irradiation showed significantly greater cytotoxicity than the treatment with DOX&HAuNS-TSL alone, DOX-TSL alone (chemotherapy alone) and HAuNS-TSL plus NIR laser irradiation (Photothermal ablation, PTA, alone). In vivo antitumor study indicated that the combination of simultaneous photothermal and chemotherapeutic effect mediated by DOX&HAuNS-TSL plus NIR laser presented a significantly higher antitumor efficacy than the PTA alone mediated by HAuNS-TSL plus NIR laser irradiation.

Conclusions

Our study could be as the valuable reference and direction for the clinical application of PTA in tumor therapy.     

丝裂霉素在兔离体角膜中的渗透特性研究

目的考察丝裂霉素在兔离体角膜中的渗透特性。方法以谷胱甘肽缓冲液为接收液,使用水平式扩散仪考察丝裂霉素在离体兔角膜中的渗透特性;样品使用HPLC测定,采用Agilent Zorbax C18柱(150 mm×4.6 mm,5μm),流动相为甲醇∶水(70∶30,v/v),流速为1 mL/min,检测波长为365 nm。结果建立的丝裂霉素HPLC测定方法专属性、线性、精密度等均良好,丝裂霉素在兔角膜中的渗透按照一级动力学拟合时相关系数最高。结论丝裂霉素在兔离体角膜中的渗透符合一级动力学过程。     

Laparoscopic anatomical portal territory hepatectomy using Glissonean pedicle approach (Takasaki approach) with indocyanine green fluorescence negative staining: how I do it

BackgroundLaparoscopic anatomical resection (LAR) is a highly challenging procedure. This study aimed to describe our experience of the LAR with an indocyanine green fluorescence negative staining (ICGNS) by the Glissonean pedicle transection (Takasaki) approach.MethodsFrom April 2017 to December 2019, 43 consecutive patients underwent LAR with ICGNS strategy in our medical team. The details of the ICGNS strategy were described. The demographic and clinicopathological data of the included patients were retrospectively analyzed.ResultsThe extent of resections included right hemihepatectomy (n = 12), left hemihepatectom (n = 4), left lateral sectionectomy (n = 3), Right anterior sectionectomy (n = 3), Right posterior sectionectomy (n = 6), central hepatectomy (n = 2), single anterolateral segmentectomy (n = 5), single posterosuperior segmentectomy (n = 6), and bisegmentectomy (n = 2). The mean operation time was 212 ± 53 min, and the median estimated blood loss was 200 (100–300) ml. The overall complication rate was 30.2% (grade I, 14%; grade II, 14%; grade III, 2.3%). The median duration of postoperative hospital stay was 6 (4–7) days.ConclusionICGNS is a safe and feasible LAR strategy that greatly facilitates selecting the liver transection plane, although its benefits need to be verified by large-sample comparative studies.     

自体脂肪游离移植在矫正面部局部凹陷性畸形中的临床应用

目的:探究自体颗粒脂肪游离移植在面部美容中的临床应用疗效,为临床上提供更为合理的治疗方案。方法:回顾性研究我院2010年2月~2012年4月,81例面部局部凹陷性畸形患者,其中观察组采用自体颗粒脂肪游离移植的方法,对照组采用硅胶进行治疗,比较两组患者的治疗效果。结果:观察组患者治疗的总有效率为90.74%,对照组患者治疗的有效率为85.52%,两组患者的治疗效率之间没有显著差异,P0.05,观察组患者不良反应的发生率为移位(0%)、排斥反应(0%)、局部红肿5.56%、局部硬结3.70%明显低于对照组14.81%、18.52%、29.63%和22.22%,P0.05。结论:自体颗粒脂肪游离移植在面部美容中具有较好的临床效果以及较少的副作用,值得推广使用。     

Reactive oxygen species up-regulates SOCS-3 in 3T3-L1 adipocytes

We investigated the effect of increased intracellular reactive oxygen species(ROS) on SOCS-3 expression in 3T3-L1 adipocytes. Increased intracellular ROS levels in 3T3-L1 adipocytes were achieved by two methods of exposure to H2O2 and the occurrence of oxidative stress in cells was assessed by flow cytometry . Expression of SOCS-3 mRNA and that of some adipokines were measured by real time PCR. The level of SOCS-3 protein was determined by western blot. The effect of the antioxidant alpha-lipoic acid was also investigated. Both the relatively mild increased intracellular ROS and the acute but transient increased ROS elevated the levels of SOCS-3 mRNA and protein in 3T3-L1 adipocytes, acompanied with elevated levels of TNF-α mRNA and resistin mRNA and the decreased levels of adiponectin mRNA and secretory adiponectin in culture medium. α-lipoic acid could attenuate the effects of ROS on 3T3-L1 adipocytes. We hypothesized that in mature 3T3-L1 adipocytes, SOCS-3 could be upregulated directly by the induction of increased intracellular ROS and to some extent which was up-regulated by adipokine modulation.

     

锁定钢板外固定治疗胫骨中下段骨折

目的：探讨锁定钢板外固定治疗胫骨中下段骨折的临床疗效。方法：自2010年1月至2013年1月,采用锁定钢板外固定治疗18例胫骨中下段骨折患者,其中男11例,女7例;年龄13~80岁,平均53.5岁;病程2 h~3 d。骨折按AO分型：A型4例,B型11例,C型3例。开放骨折6例（Gustilo分型：Ⅰ型2例,Ⅱ型3例,Ⅲ型1例）,闭合骨折12例。观察患者的手术时间、术后并发症情况,并采用Johner-Wruhs评价标准对术后疗效进行评价。结果：18例患者获随访,时间6~15个月,平均11个月。2例发生局部皮肤坏死（其中1例骨外露）,2例骨折延迟愈合（均为开放性骨折）,1例钉道感染,均无螺钉松动及折断发生。按Johner-Wruhs评价标准,优10例,良6例,可2例。结论：锁定钢板外固定是治疗胫骨中下段骨折的有效方法之一,具有手术损伤小、手术时间短、术后并发症少、功能恢复好的优点。     

Alcoholic and isocaloric diet,but not ovariectomy,influence the apoptosis of bone cells within the alveolar bone crest of rats

ObjectiveStudies suggest that chronic alcoholism as well as oestrogen deficiencies may affect bones in general, including alveolar bone and, by doing so, increase individuals’ susceptibility to develop progressive periodontal disease. This paper aims to verify the influence of chronic alcoholism and/or oestrogen deficiencies in the apoptosis of bone cells of the alveolar bone crest region in rats.DesignInitially, 54 rats were divided into ovariectomized (Ovx) and Sham operated (Sham) groups. Thirty days after surgery, these two groups were equally sub-divided, and received, for 56 days, the following dietary intervention: alcoholic diet (with 20% alcohol solution,), isocaloric diet and ad libitum diet (free diet). Analysis was undertaken by immunohistochemistry, using an antibody to detect apoptosis (anti PARP p-85).ResultsWhen comparing the six experimental groups, no significant differences were observed in the apoptosis of bone cells. Also, there was no significant difference in the quantity of cells undergoing apoptosis when the animals from Ovx groups were compared with those from Sham groups. However, when comparing only different dietary groups, differences were observed between the groups ad libitum and isocaloric, to osteoblasts (p = 0.045); and ad libitum and alcohol, to osteocytes (p = 0.007).ConclusionIt is concluded that ovariectomy was not able to influence the rate of apoptosis of bone cells of the alveolar bone crest region in rats and that a possible influence of diet on apoptosis of osteoblasts and osteocytes cannot be ruled out.     

Differential effect of hypoxia on human mesenchymal stem cell chondrogenesis and hypertrophy in hyaluronic acid hydrogels

Photocrosslinked hyaluronic acid (HA) hydrogels provide a conducive 3-D environment that supports the chondrogenesis of human mesenchymal stem cells (hMSCs). The HA macromer concentration in the hydrogels has a significant impact on the chondrogenesis of the encapsulated MSCs due to changes in the physical properties of the hydrogels. Meanwhile, hypoxia has been shown to promote MSC chondrogenesis and suppress subsequent hypertrophy. This study investigates the combinatorial effect of tuning HA macromer concentration (1.5–5% w/v) and hypoxia on MSC chondrogenesis and hypertrophy. To decouple the effect of HA concentration from that of crosslinking density, the HA hydrogel crosslinking density was adjusted by varying the extent of the reaction through the light exposure time while keeping the HA concentration constant (5% w/v at 5 or 15 min). It was found that hypoxia had no significant effect on the chondrogenesis and cartilaginous matrix synthesis of hMSCs under all hydrogel conditions. In contrast, the hypoxia-mediated positive or negative regulation of hMSC hypertrophy in HA hydrogels is dependent on the HA concentration but independent of the crosslinking density. Specifically, hypoxia significantly suppressed hMSC hypertrophy and neocartilage calcification in low HA concentration hydrogels, whereas hypoxia substantially enhanced hMSC hypertrophy, leading to elevated tissue calcification in high HA concentration hydrogels irrespective of their crosslinking density. In addition, at a constant high HA concentration, increasing hydrogel crosslinking density promoted hMSC hypertrophy and matrix calcification. To conclude, the findings from this study demonstrate that the effect of hypoxia on hMSC chondrogenesis and hypertrophy is differentially influenced by the encapsulating HA hydrogel properties.     

胎儿超声心动图检查定量11~17周正常胎儿主动脉和肺动脉内径Z-评分的初步研究

目的探讨早孕期（11^＋0周~13^＋6周）和中孕早期（14^＋0周~17^＋6周）胎儿主动脉内径（AO）与肺动脉内径（PA）与胎儿生物学生长参数的相关性,初步建立早孕期和中孕早期胎儿AO与PA的正常参考值范围及Z-评分方程,并评价方程的有效性。 方法随机选取孕周（GA）为（11^＋0周~17^＋6周）正常单胎胎儿270例,将成功显示左、右心室流出道切面的245例胎儿纳入研究,获得胎儿顶臀径（CRL）、双顶径（BPD）、股骨长径（FL）、孕周（GA）等生物学生长参数。在胎儿左、右心室流出道切面测量收缩末期AO及PA,以GA、BPD和FL作为独立自变量,AO及PA作为因变量,建立AO、PA的正常参考值范围,并对每个参数的绝对残差（SD）进行加权回归,建立Z-评分方程。 结果采用简单的线性回归模型,可以很好地描述AO和PA与非心脏生物特征参数（BPD、FL、GA）的关系。AO、PA与GA、BPD、FL均呈显著线性相关（GA与AO：r=0.9276,GA与PA：r=0.9271,BPD与AO：r=0.9551,BPD与PA：r=0.9558,FL与AO：r=0.9462,FL与PA：r=0.9483,均<0.001）,其中与BPD的相关性最强。 结论正常早孕期及中孕早期胎儿的AO、PA随着孕周的增加而增长,本研究初步建立了正常胎儿早孕期及中孕早期AO、PA的参考范围及其Z-评分方程。为早孕期及中孕早期评估胎儿大血管生长提供精确的参考标准,在早期筛查或诊断胎儿先天性心脏畸形方面具有潜在的应用价值。