经会阴二维超声对自然分娩女性产后盆底三腔室运动和早期盆底功能的评估价值

目的:探讨经会阴二维超声对自然分娩女性产后盆底三腔室运动和早期盆底功能的评估价值。方法:选取2019年2月～2019年7月于我院进行自然分娩的产妇284例作为研究组,另选取同期于我院接受诊治的未育女性200例作为对照组。两组均进行经会阴二维超声检查,比较两组静息期、张力期、缩肛期的肛管直肠连接部(ARJ)、宫颈外口(CV)、尿道膀胱连接部(UVJ)的位置及运动变化情况,对比两组静息状态下以及最大Valsaval动作下盆底超声参数。结果:研究组静息期、张力期、缩肛期的CV距离水平参照线的垂直长度(CV-VD)、UVJ距离水平参照线的垂直长度(UVJ-VD)均低于对照组(均P0.05)。研究组张力期对应静息期垂直长度△r-s CV-VD、△r-s UVJ-VD均高于对照组,而缩肛期对应静息期垂直长度△r-s CV-VD、△r-s UVJ-VD均低于对照组(均P0.05)。研究组静息状态下膀胱颈位置(BNP)低于对照组,而膀胱尿道后角(PUA)高于对照组(均P0.05);研究组最大Valsaval动作下膀胱颈移动度(BND)、PUA、尿道旋转角(URA)均高于对照组(均P0.05)。结论:经会阴二维超声可对自然分娩女性产后盆底三腔室运动和早期盆底功能进行有效观察,有助于评估女性盆底结构、功能变化,具有一定的临床推广应用价值。     

持续镇痛分娩对产妇分娩结局和新生儿评分的影响

目的:研究持续镇痛分娩对产妇分娩结局和新生儿评分的影响。方法:选择2018年7月～2019年7月中国医科大学航空总医院(本院)采取硬膜外分娩镇痛的101例产妇,将其随机分为两组。当产生确切的镇痛效果,进入第二产程后,观察组的51例产妇采用0.4μg/m L舒芬太尼以及0.08%罗哌卡因进行持续镇痛分娩;对照组的50例产妇则在宫口开全后,使用生理盐水替代泵内的局麻药物,直到分娩结束。比较两组产妇催产素的使用率,宫口扩张度和第一、第二产程按压硬膜外自控镇痛泵的次数,分娩方式,新生儿的体质量,脐动脉血pH值,出生后1 min和5 min Apgar评分,产妇修复会阴部时的视觉模拟评分(visual analogue scale, VAS)评分及产妇对于第二产程镇痛的满意度评分。结果:两组产妇催产素的使用率、宫口扩张度和第一、第二产程按压硬膜外自控镇痛泵的次数、分娩方式(剖宫产率、器械助产率、自然分娩率)、第一产程镇痛时间、第一以及第二产程时间相比均无显著差异(P0.05);两组新生儿的体质量,脐动脉血pH值,出生后1 min和5 min Apgar评分小于8分的新生儿所占的比例相比没有明显的差异(P0.05);观察组产妇修复会阴部时的VAS评分明显低于对照组(P0.05),产妇对于第二产程镇痛的满意度评分明显高于对照组(P0.05)。结论:持续镇痛分娩对产妇分娩结局和新生儿评分无明显的影响,但可显著提高产妇对第二产程镇痛和修复会阴部时镇痛的满意度。     

Improved therapeutic efficiency of photothermal treatment and nursing care in prostate cancer by DOX loaded PEG coated Cu@Se nano-hybrid vesicle

Cancer is one of the major life threatening diseases, with higher mortality rate and morbidity. It is always a challenge for effective drug delivery and release of drug in specific tumor sites. Therefore to identify the synergistic effect of chemotherapeutic drug and photo thermal agent on tumor area, Doxorubicin (DOX) acts as anticancer agent but it has low aqueous solubility so its clinical application is limited. The present study developed doxorubicin (DOX) were designed to be with the poly ethylene glycol (PEG) functionalized copper and selenium (Cu-Se) nanoparticles (PEG@Cu-Se+DOX) and it is efficiently synthesized and enhance its aqueous formulation and improve the prostate cancer (DU145 and LNCaP) activity. The characteristics like mono dispersity, size stability and constant spectral of as-synthesized nanoparticles are comparably excellent than DOX alone. Also the enhanced cellular uptake and in vitro cytoxicicty suggests these nanoparticles selectively killing prostate cancer. In this present study explained that PEG@Cu-Se+DOX as a safe and hopeful strategy for chemotherapeutics of photothermal therapy and deserve for further clinical evaluations.     

Gene transfer to skeletal muscle using hydrodynamic limb vein injection: current applications,hurdles and possible optimizations

Hydrodynamic limb vein injection is an in vivo locoregional gene delivery method. It consists of administrating a large volume of solution containing nucleic acid constructs in a limb with both blood inflow and outflow temporarily blocked using a tourniquet. The fast, high pressure delivery allows the musculature of the whole limb to be reached. The skeletal muscle is a tissue of choice for a variety of gene transfer applications, including gene therapy for Duchenne muscular dystrophy or other myopathies, as well as for the production of antibodies or other proteins with broad therapeutic effects. Hydrodynamic limb vein delivery has been evaluated with success in a large range of animal models. It has also proven to be safe and well‐tolerated in muscular dystrophy patients, thus supporting its translation to the clinic. However, some possible limitations may occur at different steps of the delivery process. Here, we have highlighted the interests, bottlenecks and potential improvements that could further optimize non‐viral gene transfer following hydrodynamic limb vein injection.     

Experimental models of maternal–fetal interface and their potential use for nanotechnology applications

During pregnancy, the placenta regulates the transfer of oxygen, nutrients, and residual products between the maternal and fetal bloodstreams and is a key determinant of fetal exposure to xenobiotics from the mother. To study the disposition of substances through the placenta, various experimental models are used, especially the perfused placenta, placental villi explants, and cell lineage models. In this context, nanotechnology, an area of study that is on the rise, enables the creation of particles on nanometric scales capable of releasing drugs aimed at specific tissues. An important reason for furthering the studies on transplacental transfer is to explore the potential of nanoparticles (NPs), in new delivery strategies for drugs that are specifically aimed at the mother, the placenta, or the fetus and that involve less toxicity. Due to the fact that the placental barrier is essential for the interaction between the maternal and fetal organisms as well as the possibility of NPs being used in the treatment of various pathologies, the aim of this review is to present the main experimental models used in studying the maternal–fetal interaction and the action of NPs in the placental environment.     

Structure comparison of the chimeric AAV2.7m8 vector with parental AAV2

The AAV2.7m8 vector is an engineered capsid with a 10-amino acid insertion in adeno-associated virus (AAV) surface variable region VIII (VR-VIII) resulting in the alteration of an antigenic region of AAV2 and the ability to efficiently transduce retina cells following intravitreal administration. Directed evolution and in vivo screening in the mouse retina isolated this vector. In the present study, we sought to identify the structural differences between a recombinant AAV2.7m8 (rAAV2.7m8) vector packaging a GFP genome and its parental serotype, AAV2, by cryo-electron microscopy (cryo-EM) and image reconstruction. The structures of rAAV2.7m8 and AAV2 were determined to 2.91 and 3.02 Å resolution, respectively. The rAAV2.7m8 amino acid side-chains for residues 219–745 (the last C-terminal residue) were interpretable in the density map with the exception of the 10 inserted amino acids. While observable in a low sigma threshold density, side-chains were only resolved at the base of the insertion, likely due to flexibility at the top of the loop. A comparison to parental AAV2 (ordered from residues 217–735) showed the structures to be similar, except at some side-chains that had different orientations and, in VR-VIII containing the 10 amino acid insertion. VR-VIII is part of an AAV2 antigenic epitope, and the difference is consistent with rAAV2.7m8′s escape from a known AAV2 monoclonal antibody, C37-B. The observations provide valuable insight into the configuration of inserted surface peptides on the AAV capsid and structural differences to be leveraged for future AAV vector rational design, especially for retargeted tropism and antibody escape.     

Advancing Aptamers as Molecular Probes for Cancer Theranostic Applications—The Role of Molecular Dynamics Simulation

Theranostics cover emerging technologies for cell biomarking for disease diagnosis and targeted introduction of drug ingredients to specific malignant sites. Theranostics development has become a significant biomedical research endeavor for effective diagnosis and treatment of diseases, especially cancer. An efficient biomarking and targeted delivery strategy for theranostic applications requires effective molecular coupling of binding ligands with high affinities to specific receptors on the cancer cell surface. Bioaffinity offers a unique mechanism to bind specific target and receptor molecules from a range of non‐targets. The binding efficacy depends on the specificity of the affinity ligand toward the target molecule even at low concentrations. Aptamers are fragments of genetic materials, peptides, or oligonucleotides which possess enhanced specificity in targeting desired cell surface receptor molecules. Aptamer–target binding results from several inter‐molecular interactions including hydrogen bond formation, aromatic stacking of flat moieties, hydrophobic interaction, electrostatic, and van der Waals interactions. Advancements in Systematic Evolution of Ligands by Exponential Enrichment (SELEX) assay has created the opportunity to artificially generate aptamers that specifically bind to desired cancer and tumor surface receptors with high affinities. This article discusses the potential application of molecular dynamics (MD) simulation to advance aptamer‐mediated receptor targeting in targeted cancer therapy. MD simulation offers real‐time analysis of the molecular drivers of the aptamer‐receptor binding and generate optimal receptor binding conditions for theranostic applications. The article also provides an overview of different cancer types with focus on receptor biomarking and targeted treatment approaches, conventional molecular probes, and aptamers that have been explored for cancer cells targeting.     

Biotin and glucose dual-targeting,ligand-modified liposomes promote breast tumor-specific drug delivery

Breast cancer is the second leading cause of cancer-related deaths in women. Ligand-modified liposomes are used for breast tumor-specific drug delivery to improve the efficacy and reduce the side effects of chemotherapy; however, only a few liposomes with high targeting efficiency have been developed because the mono-targeting, ligand-modified liposomes are generally unable to deliver an adequate therapeutic dose. In this study, we designed biotin-glucose branched ligand-modified, dual-targeting liposomes (Bio-Glu-Lip) and evaluated their potential as a targeted chemotherapy delivery system in vitro and in vivo. When compared with the non-targeting liposome (Lip), Bio-Lip, and Glu-Lip, Bio-Glu-Lip had the highest cell uptake in 4T1 cells (3.00-fold, 1.60-fold, and 1.95-fold higher, respectively) and in MCF-7 cells (2.63-fold, 1.63-fold, and 1.85-fold higher, respectively). The subsequent cytotoxicity and in vivo assays further supported the dual-targeting liposome is a promising drug delivery carrier for the treatment of breast cancer.     

Improving NK1R-targeted gene delivery of stearyl-antimicrobial peptide CAMEL by conjugating it with substance P

Specificity is a crucial condition that hampers the application of non-viral vectors for cancer gene therapy. In a previous study, we developed an efficient gene vector, stearyl-CAMEL, using N-terminal stearylation of the antimicrobial peptide CAMEL. Substance P (SP), an 11-residue neuropeptide, rapidly enters cells after binding to the neurokinin-1 receptor (NK1R), which is expressed in many cancer cell lines. In this study, the NK1R-targeted gene vector stearyl-CMSP was constructed by conjugating SP to the C-terminus of stearyl-CAMEL. Our results indicated that stearyl-CMSP displayed significant transfection specificity for NK1R-expressing cells compared with that shown by stearyl-CAMEL. Accordingly, the stearyl-CMSP/p53 plasmid complexes had significantly higher antiproliferative activity against HEK293-NK1R cells than they did against HEK293 cells, while the stearyl-CAMEL/p53 plasmid complexes did not show this specificity in antiproliferative activity. Consequently, conjugation of the NK1R-targeted ligand SP is a simple and successful strategy to construct efficient cancer-targeted non-viral gene vectors.