Adjacent skin rotation flap for large defect in primary breast tumor.

BACKGROUNDS: Surgical resection of large primary breast tumor often results in large chest wall defects. The purpose of this study is to evaluate the feasibility of using adjacent skin rotation (ASR) flap in patients with giant primary breast tumor. METHODS: A total of 26 giant primary breast tumor patients treated with ASR flap were included in this study. The postoperative conditions, including operating time, blood loss, length of hospital stay, and clinical complications were observed. Meanwhile, the information on 17 breast tumor patients treated with transverse rectus abdominis myocutaneous (TRAM) flap were collected and assigned to a control group. RESULTS: The mean defect size after mastectomy was 16.7 × 13.4 cm, while the median follow-up period was 13 months after surgery. A total of 15.4% patients had developed with local complications, and one of them had more than one complication. When comparing the postoperative outcomes, statistically significant differences were found between the two groups with respect to operating time, blood loss, and length of hospital stay (P < 0.001). CONCLUSIONS: ASR flap is a reliable technique for immediate reconstruction of massive chest wall defects in patients with giant primary breast tumor.

Redundant mechanisms for vascular growth factors in retinopathy of prematurity in vitro.

BACKGROUND: Current treatments for retinopathy of prematurity (ROP) targeting single vascular growth factors are ineffective in preventing neoangiogenesis. METHODS: We investigated the redundant/compensatory mechanisms between vascular growth factors in ROP. Cultured retinal vascular endothelial cells under CoCl2-induced hypoxia were transfected with recombinant adeno-associated virus type 2-vascular endothelial growth factor (VEGF) or pGIPZ-VEGF RNA interference to up- and downregulate VEGF expression, respectively. At 48 h after transfection, basic fibroblast growth factor (bFGF) and angiopoietin 1 (ANG1) gene expression as well as mitotic cycle changes were analyzed in the cells and correlated with the change in VEGF expression. RESULTS: Compared with the normal control group 1, at 30 min, 12 h and 24 h, the expressions of VEGF, bFGF and ANG1 in the hypoxia control group 2 were significantly higher. In the highly expressing VEGF group (group 3), the expressions of bFGF and ANG1 were downregulated, while in the low-expressing VEGF group 4, the expressions of bFGF and ANG1 were significantly upregulated. In the bevacizumab treatment group 5, the expressions of VEGF, bFGF and ANG1 were similar to those in group 2, and the difference was not significant. CONCLUSIONS: A compensatory mechanism (redundancy) exists between vascular growth factors in ROP. Such a phenomenon could partially explain why the inhibition of a single growth factor cannot effectively prevent the recurrence of neovascularization in ROP. A more effective strategy for treating ROP may be to inhibit VEGF and its redundant pathways.

Hydrophobic Metal-Organic Frameworks: Assessment, Construction, and Diverse Applications.

Tens of thousands of metal-organic frameworks (MOFs) have been developed in the past two decades, and only ≈100 of them have been demonstrated as porous and hydrophobic. These hydrophobic MOFs feature not only a rich structural variety, highly crystalline frameworks, and uniform micropores, but also a low affinity toward water and superior hydrolytic stability, which make them promising adsorbents for diverse applications, including humid CO2 capture, alcohol/water separation, pollutant removal from air or water, substrate-selective catalysis, energy storage, anticorrosion, and self-cleaning. Herein, the recent research advancements in hydrophobic MOFs are presented. The existing techniques for qualitatively or quantitatively assessing the hydrophobicity of MOFs are first introduced. The reported experimental methods for the preparation of hydrophobic MOFs are then categorized. The concept that hydrophobic MOFs normally synthesized from predesigned organic ligands can also be prepared by the postsynthetic modification of the internal pore surface and/or external crystal surface of hydrophilic or less hydrophobic MOFs is highlighted. Finally, an overview of the recent studies on hydrophobic MOFs for various applications is provided and suggests the high versatility of this unique class of materials for practical use as either adsorbents or nanomaterials.

High Anisotropy in Tubular Layered Exfoliated KP15.

Two-dimensional (2D) materials with high anisotropic properties, such as black phosphorus and ReS2, show amazing potential for applications in future nanoelectronic and optoelectronic devices. However, degradation of black phosphorus under ambient conditions and the expensiveness of Re block their application. In this study, another layered material, KP15, that has highly anisotropic properties was successfully prepared. The detailed crystal structure and electron-density distribution calculation reveal that KP15 exhibits an anisotropic layered structure with two rows of P tubes connected by K atoms that are antiparallel in a single layer. Outstanding chemical stability, angular dependence of the Raman response, excitation, and exciton emission at room temperature have been found in exfoliated KP15 nanoribbons. Importantly, the exciton emission at room temperature suggests the existence of a large exciton binding energy. Our results indicate that, because this layered material, KP15, has high anisotropic properties and ultrachemical stability and is derived from abundant raw materials, it has great potential for applications in optoelectronic devices.

Expression of angiogenic growth factors VEGF, bFGF and ANG1 in colon cancer after bevacizumab treatment in vitro: A potential self-regulating mechanism.

The present study aimed to examine changes in the expression of angiogenic growth factors in vascular endothelial cells isolated from colon cancer after bevacizumab treatment in vitro, and to explore a potential mechanism of their self-regulation as a possible mechanism for antiangiogenic therapy failure in clinics. Vascular endothelial cells were isolated from tumors of colon cancer patients and transfected with recombinant adeno-associated virus type 2-vascular endothelial growth factor (VEGF) or pGIPZ-VEGF RNA interference in order to upregulate or downregulate VEGF expression. Changes in VEGF expression and its correlation with the expression of angiogenesis-related factors, including basic fibroblast growth factor (bFGF) and angiopoietin 1 (ANG1), after treatment with bevacizumab in vitro, were investigated. The results showed that in cells with VEGF overexpression, bFGF and ANG1 were downregulated, whereas in cells in which VEGF was knocked down, upregulation of bFGF and ANG1 was detected. In cells treated with bevacizumab, a significant upregulation of VEGF and downregulation of bFGF and ANG1 were observed. Our data indicate that after bevacizumab treatment, a potential self-regulating mechanism of angiogenic growth factors in colon cancer-derived endothelial cells is activated, which may explain why current antiangiogenic therapy with bevacizumab has limited effects in prolonging the survival of colon cancer patients.

[Prokaryotic expression, purification and characterization of arginine kinase of Bombyx mori].

Arginine kinase (AK) is a key enzyme in energy metabolism of invertebrates and plays an important regulatory role in the life activities such as growth and development, nutrition utilization, immune resistance and stress response. Arginine kinase of Bombyx mori (BmAK) is related to the energy balance and anti-NPV process, but there is little research on its molecular structure and enzymatic properties. We cloned the ORF sequence of BmAK gene, and analyzed chromosomal localization, genomic structure, mRNA structure, secondary and tertiary structure. Phylogenetic analysis indicated that AK was highly conserved in evolution. Soluble recombinant BmAK was obtained by prokaryotic expression, and purified by Ni-NTA affinity chromatography. The circular dichroism spectroscopy showed that BmAK contained α-helix structures, and its α-helix structures were relatively stable in the pH range between 5 and 10. Enzyme activity analysis showed that the optimum temperature of BmAK was 30 ℃ and the optimum pH of BmAK was 7.5. The optimal temperature of BmAK was 25 ℃. Between 15 ℃ and 30 ℃, the structure and activity of BmAK was relatively stable. The structure of BmAK was relatively stable at pH 7.0. Our findings reveal the structure and function of BmAK to develop novel green safe and environmentally friendly insecticides.

Evaluation of Leber's hereditary optic neuropathy patients prior to a gene therapy clinical trial.

Gene therapy may be a promising approach for the treatment of Leber hereditary optic neuropathy. The aim of this study was to evaluate patients with this condition who were recruited into an upcoming gene therapy clinical trial and to assess any changes in the detection parameters to provide support for the clinical trial. Sixteen patients with Leber hereditary optic neuropathy were evaluated using visual function tests 12 months before the initiation of gene therapy. Then, the results of visual acuity (VA), visual field (VF), RNFL (retinal nerve fiber layer) thickness, and Pattern-reversal Visual evoked potential (PR-VEP) were compared and analyzed. A total of 32 eyes of 16 patients were evaluated. Based on the best-corrected visual acuity (BCVA), 24 eyes were relatively stable compared with the baseline evaluation, and 8 eyes had significant changes, including 5 eyes that showed improvement and 3 eyes that showed impairment. In all eyes, the changes in the best-corrected visual acuity were significantly correlated with the changes in the visual field index (VFI), mean defect (MD), and P100 of the visual evoked potential. In the eyes with relatively stable BCVA and those with an obvious improvement in the BCVA, only the visual mean defect showed a significant change; the other indicators were not significantly different. Aside from the patients showing a tendency of spontaneous improvement, the others were in accordance with the requirement. The effects of Leber hereditary optical neuropathy (LHON) gene therapy should be evaluated primarily based on visual acuity. Additionally, visual field, neural fiber thickness, and electrophysiology should be considered in the evaluation.

Long-term outcomes of gene therapy for the treatment of Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy (LHON) is a disease that leads to blindness. Gene therapy has been investigated with some success, and could lead to important advancements in treating LHON. This was a prospective, open-label trial involving 9 LHON patients at Tongji Hospital, Wuhan, China, from August 2011 to December 2015. The purpose of this study was to evaluate the long-term outcomes of gene therapy for LHON. Nine LHON patients voluntarily received an intravitreal injection of rAAV2-ND4. Systemic examinations and visual function tests were performed during the 36-month follow-up period to determine the safety and efficacy of this gene therapy. Based on successful experiments in an animal model of LHON, 1 subject also received an rAAV2-ND4 injection in the second eye 12months after gene therapy was administered in the first eye. Recovery of visual acuity was defined as the primary outcome of this study. Changes in the visual field, visual evoked potential (VEP), optical coherence tomography findings, liver and kidney function, and antibodies against AAV2 were defined as secondary endpoints. Eight patients (Patients 2-9) received unilateral gene therapy and visual function improvement was observed in both treated eyes (Patients 4, 6, 7, and 8) and untreated eyes (Patients 2, 3, 4, 6 and 8). Visual regression fluctuations, defined as changes in visual acuity greater than or equal to 0.3 logMAR, were observed in Patients 2 and 9. Age at disease onset, disease duration, and the amount of remaining optic nerve fibers did not have a significant effect on the visual function improvement. The visual field and pattern reversal VEP also improved. The patient (Patient 1) who received gene therapy in both eyes had improved visual acuity in the injected eye after the first treatment. Unfortunately, visual acuity in this eye decreased 3months after he received gene therapy in the second eye. Animal experiments suggested that ND4 expression remains stable in the contralateral eye after intravitreal injections. No serious safety problem was observed in the 3-year follow-up of the 9 participants enrolled in this virus-based gene therapy. Meanwhile, our results support the use of intravitreal rAAV2-ND4 as an aggressive maneuver in our clinical trial. Further study in additional patients and in these 9 subjects is needed to better understand the effects of rAAV2-ND4 gene therapy on LHON and to increase the applications of this technique.

Efficacy and Safety of rAAV2-ND4 Treatment for Leber's Hereditary Optic Neuropathy.

Leber's hereditary optic neuropathy (LHON) is a mitochondrially inherited disease leading to blindness. A mitochondrial DNA point mutation at the 11778 nucleotide site of the NADH dehydrogenase subunit 4 (ND4) gene is the most common cause. The aim of this study was to evaluate the efficacy and safety of a recombinant adeno-associated virus 2 (AAV2) carrying ND4 (rAAV2-ND4) in LHON patients carrying the G11778A mutation. Nine patients were administered rAAV2-ND4 by intravitreal injection to one eye and then followed for 9 months. Ophthalmologic examinations of visual acuity, visual field, and optical coherence tomography were performed. Physical examinations included routine blood and urine. The visual acuity of the injected eyes of six patients improved by at least 0.3 log MAR after 9 months of follow-up. In these six patients, the visual field was enlarged but the retinal nerve fibre layer remained relatively stable. No other outcome measure was significantly changed. None of the nine patients had local or systemic adverse events related to the vector during the 9-month follow-up period. These findings support the feasible use of gene therapy for LHON.