Molecular targeting of liposomal nano-particles to lymphatic system

Conventional liposomal drug delivery has been associated with obvious limitations, such as a rapid absorption by the recticulo-endothelial system in the liver and spleen, a short circulation time and a low therapeutic efficacy. Various modifications of liposomal drugs have been developed to prolong the duration of actions of the drugs at target sites, reduce its adverse effects and increase therapeutic index of drugs such as polymeric conjugation and polymeric fixation on the surface of a liposome. The lymphatic system is an important highway to spread the metastasis of most human cancers including breast, colon, and lung, ovarian and prostate. To eradicate those metastatic cancer cells from the lymphatic system, several efforts have been made to develop new and efficient lymphatic targeting drug delivery systems in order to achieve a high initial lymphatic uptake and lymph node localization. Recently, molecule targeting of liposome to lymphatic system may enhance therapeutic efficacy by improving the initial lymphatic uptake and the lymph nodal retention of liposomes such as the ligand-receptor and antibodies binding on the surface of liposome. This article aims to review the emerging liposomal drug, which is targeting the lymphatic system. The significant factors associated with targeting liposomal drugs will also be discussed in more detail in this review.     

定量组织速度成像技术评价阿霉素诱导兔心肌病模型：与常规经胸超声心动图比较

目的:采用定量组织速度成像技术评价阿霉素诱导兔心肌病模型,并与常规经胸超声心动图比较其评估优势。方法:实验于2005-06/2006-08在大连医科大学完成。①实验分组及处理:取纯种新西兰白兔22只,雌雄不限,随机分成阿霉素组12只,给予阿霉素每次2mg/kg,以1g/L耳缘静脉注射,每周1次,注射8周;对照组10只每周注射2mL/kg生理盐水,共8周。②实验评估:每周应用HPSonos5500型彩色多普勒超声诊断仪(美国Agilent公司生产)对两组兔心脏进行左室收缩末期和舒张末期内径明、室间隔厚度、E峰、射血分数、左室短轴缩短率等常规超声参数测量,使用GEVivid7型彩色多普勒超声诊断仪(美国GE公司生产)进行收缩期和舒张期峰值速度、收缩期加速度定量组织速度成像参数测定。结果:22只兔进入统计。①对照组1～12周各参数与阿霉素组基础状态下比较无明显差异(P>0.05)。②第4周阿霉素组二尖瓣环运动的平均收缩期和舒张期峰值速度、收缩期加速度较基础状态明显减低(P均<0.05)。③第7周阿霉素组二尖瓣环运动的收缩期和舒张期峰值速度、收缩期加速度较基础状态明显减低(P<0.01),E峰较基础状态明显减低(P<0.05)。④第8周阿霉素组二尖瓣环运动的收缩期和舒张期峰值速度、收缩期加速度较基础状态明显减低(P<0.01),E峰较基础状态明显减低(P<0.01),左室收缩末期和舒张末期内径明显增大(P<0.05)。⑤第12周阿霉素组二尖瓣环运动的收缩期和舒张期峰值速度、收缩期加速度较基础状态明显减低(P<0.01),左室收缩末期和舒张末期内径明显增大(P<0.01),室间隔厚度、左室后壁厚度明显变薄(P<0.05),射血分数、左室短轴缩短率和E峰明显减低(P<0.01)。结论:定量组织速度成像参数可有效评价阿霉素诱导心肌病模型兔心肌的病理变化,较常规超声参数更敏感。     

大鼠颈动脉球囊损伤后管壁血管内皮生长因子和血管内皮细胞黏附分子1表达及雷公藤多甙的干预

目的:观察不同剂量雷公藤多甙对颈动脉球囊损伤后大鼠血管内皮生长因子、血管内皮细胞黏附分子1的影响,探讨雷公藤多甙在再狭窄防治方面的作用。方法:实验于2006-01/05在上海复旦大学医学院动物实验中心及上海瑞金医院烧伤研究所完成。①实验材料:SPF级SD雄性大鼠32只;雷公藤多甙(复旦复华药业)。②实验分组:随机分为正常对照组、模型组、雷公藤多甙小剂量组、大剂量组各8只。③实验干预:采用右颈动脉内膜剥脱法制备大鼠颈动脉狭窄模型。模型组术后予蒸馏水3mL/(kg·d)灌胃,雷公藤多甙小剂量和大剂量组分别给予雷公藤多甙30,60mg/(kg·d)灌胃。④实验评估:于术后2周麻醉后处死各实验组动物,取材,采用免疫组织化学方法检测大鼠颈总动脉血管内皮生长因子和血管内皮细胞黏附分子1含量。结果:32只大鼠全部进入结果分析。①正常大鼠颈动脉血管壁少量表达血管内皮生长因子,球囊损伤后表达量增加,雷公藤多甙大、小剂量组血管内皮生长因子表达的趋势与模型组基本相同,但表达量较模型组明显增加,雷公藤多甙小剂量组与模型组比较,P<0.05;大剂量组与模型组相比,P<0.01。②正常大鼠颈动脉管壁少量表达血管内皮细胞黏附分子1。球囊损伤后,模型组管壁血管内皮细胞黏附分子1表达增加;雷公藤多甙小剂量组和大剂量组管壁血管内皮细胞黏附分子1表达的趋势与模型组基本相同,但数量明显下降,雷公藤多甙小剂量组与模型组比较,P<0.05,大剂量组与模型组比较P<0.01。结论:雷公藤多甙能有效促进内皮细胞生成,减少内皮细胞间的黏附,对大鼠血管球囊损伤后的狭窄有一定的防治作用。     

Entanglement-assisted concatenated quantum codes

Entanglement-assisted concatenated quantum codes (EACQCs), constructed by concatenating two quantum codes, are proposed. These EACQCs show significant advantages over standard concatenated quantum codes (CQCs). First, we prove that, unlike standard CQCs, EACQCs can beat the nondegenerate Hamming bound for entanglement-assisted quantum error-correction codes (EAQECCs). Second, we construct families of EACQCs with parameters better than the best-known standard quantum error-correction codes (QECCs) and EAQECCs. Moreover, these EACQCs require very few Einstein–Podolsky–Rosen (EPR) pairs to begin with. Finally, it is shown that EACQCs make entanglement-assisted quantum communication possible, even if the ebits are noisy. Furthermore, EACQCs can outperform CQCs in entanglement fidelity over depolarizing channels if the ebits are less noisy than the qubits. We show that the error-probability threshold of EACQCs is larger than that of CQCs when the error rate of ebits is sufficiently lower than that of qubits. Specifically, we derive a high threshold of 47% when the error probability of the preshared entanglement is 1% to that of qubits.

Quantum error-correction codes (QECCs) are necessary to realize quantum communications and to make fault-tolerant quantum computers (1, 2). The stabilizer formalism provides a useful way to construct QECCs from classical codes, but certain orthogonality constraints are required (3). The entanglement-assisted (EA) QECC (EAQECC) (4–6) generalizes the stabilizer code. By presharing some entangled states between the sender (Alice) and the receiver (Bob), EAQECCs can be constructed from any classical linear codes without the orthogonality constraints. Therefore, the construction could be greatly simplified. As an important physical resource, entanglement can boost the classical information capacity of quantum channels (7–12). Recently, it has been shown that EAQECCs can violate the nondegenerate quantum Hamming bound (13) or the quantum Singleton bound (14).Compared to standard QECCs, EAQECCs must establish some amount of entanglement before transmission. This preshared entanglement is the price to be paid for enhanced communication capability. In a sense, we need to consider the net transmission of EAQECCs—i.e., the number of qubits transmitted minus that of ebits preshared. Further, it is difficult to preserve too many noiseless ebits in EAQECCs at present. Thus, we have to use as few ebits as possible to conduct the communication—e.g., one or two ebits are preferable (15–18). In addition, EAQECCs with positive net transmission and little entanglement can lead to catalytic quantum codes (4, 6), which are applicable to fault-tolerant quantum computation (FTQC). In ref. 4, a table of best-known EAQECCs of length up to 10 was established through computer search or algebraic methods. Several EAQECCs in ref. 4 have larger minimum distances than the best-known standard QECCs of the same length and net transmission. However, for larger code lengths, the efficient construction of EAQECCs with better parameters than standard QECCs is still unknown.In classical coding theory, concatenated codes (CCs), originally proposed by Forney in the 1960s (19), provide a useful way of constructing long codes from short ones. CCs can achieve very large coding gains with reasonable encoding and decoding complexity (20). Moreover, CCs can have large minimum distances since the distances of the component codes are multiplied. As a result, CCs have been widely used in many digital communication systems—e.g., the NASA standard for the Voyager program (21) and the compact disc (20). Similarly, in QECCs, the concatenated quantum codes (CQCs), introduced by Knill and Laflamme in 1996 (22), are also effective for constructing good quantum codes. In particular, it has been shown that CQCs are of great importance in realizing FTQC (23–25).Moreover, there exists a specific phenomenon in QECCs, called “error degeneracy,” which distinguishes quantum codes from classical ones in essence. It is widely believed that degenerate codes can correct more quantum errors than nondegenerate ones. Indeed, there are some open problems concerning whether degenerate codes can violate the nondegenerate quantum Hamming bound (26) or can improve the quantum-channel capacity (27, 28). Many CQCs have been shown to be degenerate, even if the component codes are nondegenerate—e.g., Shor’s [[9,1,3]] code and the [[25,1,9]] CQC (23, 29). If we introduce extra entanglement to CQCs, it is possible to improve the error-degeneracy performance of CQCs.In this article, we generalize the idea of concatenation to EAQECCs and propose EACQCs. We show that EACQCs can beat the nondegenerate quantum Hamming bound, while standard CQCs cannot. Several families of degenerate EACQCs that can surpass the nondegenerate Hamming bound for EAQECCs are constructed. The same conclusion could be reached for asymmetric error models, in which the phase-flip errors (Z errors) happen more frequently than the bit-flip errors (X errors) (30, 31). Furthermore, we derive a number of EACQCs with better parameters than the best-known QECCs and EAQECCs. In particular, we see that many EACQCs have positive net transmission, and each of them consumes only one or two ebits. Thus, they give rise to catalytic EACQCs with little entanglement and better parameters than the best-known QECCs. Further, we show that the EACQC scheme makes EA quantum communication possible, even if the ebits are noisy. We compute the entanglement fidelity (EF) of the [[15,1,9;10]] EACQC by using Bowen’s [[3,1,3;2]] EAQECC (32) or the [[3,1,3;2]] EA repetition code (4, 6) as the inner code. The outer code is the standard [[5,1,3]] stabilizer code. We show that the [[15,1,9;10]] EACQC performs much better than the [[25,1,9]] CQC over depolarizing channels if the ebits suffer a lower error rate than the qubits. Moreover, we compute the error-probability threshold of EACQCs, and we show that EACQCs have much higher thresholds than CQCs when the error rate of ebits is sufficiently lower than that of qubits.     

Wettability and Surface Roughness of Parylene C on Three-Dimensional-Printed Photopolymers

The use of poly-(para-chloro-xylylene) (Parylene C) in microelectromechanical systems and medical devices has increased rapidly. However, little research has been conducted on the wettability and surface roughness of Parylene C after being soaked in solutions. In this study, the contact angle and surface roughness (arithmetic average of roughness) of Parylene C on three-dimensional (3D)-printed photopolymer in 10% sodium hydroxide, 10% ammonium hydroxide, and 100% phosphate-buffered saline (PBS) solutions were investigated using a commercial contact angle measurement system and laser confocal microscope, respectively. The collected data indicated that 10% ammonium hydroxide had no major effect on the contact angle of Parylene C on a substrate, with a Shore A hardness of 50. However, 10% sodium hydroxide, 10% ammonium hydroxide, and 100% PBS considerably affected the contact angle of Parylene C on a substrate with a Shore A hardness of 85. Substrates with Parylene C coating exhibited lower surface roughness than uncoated substrates. The substrates coated with Parylene C that were soaked in 10% ammonium hydroxide exhibited high surface roughness. The aforementioned results indicate that 3D-printed photopolymers coated with Parylene C can offer potential benefits when used in biocompatible devices.     

Correlation between Serum 25-Hydroxyvitamin D Level and Peripheral Arterial Stiffness in Chronic Kidney Disease Stage 3–5 Patients

Vitamin D deficiency and high brachial-ankle pulse wave velocity (baPWV) are each independently associated with higher incidence of mortality and cardiovascular (CV) disease or CV events, respectively. This study aimed to evaluate the relationship between serum 25-hydroxyvitamin D levels and baPWV in non-dialysis patients with stage 3–5 chronic kidney disease (CKD). We enrolled 180 CKD patients. A commercial enzyme-linked immunosorbent assay was used to measure 25-hydroxyvitamin D levels. BaPWV values were measured using an automatic pulse wave analyzer. Either left or right baPWV > 18.0 m/s was considered indicative of peripheral arterial stiffness (PAS). In this study, 73 (40.6%) patients were found to have PAS. Compared to those without PAS (control group), patients with PAS were older and had higher incidence of diabetes mellitus, higher systolic and diastolic blood pressure, higher levels of intact parathyroid hormone, and C-reactive protein, and lower levels of 25-hydroxyvitamin D. Multivariate logistic regression analysis found 25-hydroxyvitamin D levels (odds ratio [OR]: 0.895, 95% confidence interval [CI] 0.828–0.968, p = 0.005) and old age (OR: 1.140, 95% CI 1.088–1.194, p < 0.001) to be independently associated with PAS in patients with stage 3–5 CKD. Lower serum 25-hydroxyvitamin D levels and older age were associated with PAS in these patients.     

Utilizing Edible Agar as a Carrier for Dual Functional Doxorubicin-Fe3O4 Nanotherapy Drugs

The purpose of this study was to use agar as a multifunctional encapsulating material to allow drug and ferromagnetism to be jointly delivered in one nanoparticle. We successfully encapsulated both Fe₃O₄ and doxorubicin (DOX) with agar as the drug carrier to obtain DOX-Fe₃O₄@agar. The iron oxide nanoparticles encapsulated in the carrier maintained good saturation of magnetization (41.9 emu/g) and had superparamagnetism. The heating capacity test showed that the specific absorption rate (SAR) value was 18.9 ± 0.5 W/g, indicating that the ferromagnetic nanoparticles encapsulated in the gel still maintained good heating capacity. Moreover, the magnetocaloric temperature could reach 43 °C in a short period of five minutes. In addition, DOX-Fe₃O₄@agar reached a maximum release rate of 85% ± 3% in 56 min under a neutral pH 7.0 to simulate the intestinal environment. We found using fluorescent microscopy that DOX entered HT-29 human colon cancer cells and reduced cell viability by 66%. When hyperthermia was induced with an auxiliary external magnetic field, cancer cells could be further killed, with a viability of only 15.4%. These results show that agar is an efficient multiple-drug carrier, and allows controlled drug release. Thus, this synergic treatment has potential application value for biopharmaceutical carrier materials.     

Associations of placental weight with maternal and cord blood hormones

PurposePlacental weight has been associated with mammographic pattern and coronary heart disease in the adult offspring, but the mechanisms are unknown. We evaluated the associations of maternal and cord blood hormones with placental weight in normal pregnancies.MethodsProspective study of 167 normal singleton pregnancies in Boston, USA and 256 in Shanghai, China. Maternal hormone levels at the 27th gestational week were available for all pregnancies. Cord blood measurements were available for 86 pregnancies in Boston and 104 in Shanghai. Pearson partial correlation coefficients of log-transformed hormone levels with placental weight were calculated.ResultsMaternal levels of estriol, testosterone, and progesterone (P < .05) were positively associated with placental weight. There was no such evidence for adiponectin, prolactin, and insulin-like growth factor (IGF)-I. Cord blood steroids tended to be inversely associated with placental weight, the results being statistically significant for testosterone (P < .05). There was a marginally significant positive association of cord blood IGF-I with placental weight. Reported results were adjusted for study center.ConclusionsPlacental weight appears to be positively correlated with maternal steroids. Its correlation with cord blood steroids, however, appears inverse, compatible with negative feedback mechanisms. There is also a suggestion for placental weight to be positively associated with cord blood IGF-I.