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Li Q.,452nd Hospital of Peoples Liberation Army | Li Q.,University of Sichuan | Szatmary P.,University of Liverpool | Liu Y.,University of Sichuan | And 6 more authors.
PLoS ONE | Year: 2015

Therapy advances are constantly improving survival rates of cancer patients, however the toxic effects of chemotherapy drugs can seriously affect patients' quality of life. In women, fertility and premature ovarian endocrine dysfunction are of particular concern. It is urgently we find methods to preserve or reconstruct ovarian function for these women. This study compares GnRHa treatment with ovarian tissue cryopreservation and orthotopic transplantation in a chemotherapy-induced ovarian damage murine model. 56 inbred Lewis rats were divided into 4 treatment groups: Saline control (group I); cyclophosphamide only (group II); cyclophosphamide plus GnRHa (group III); cyclophosphamide and grafting of thawed cryopreserved ovaries (group IV). Body weight, estrous cycle recovery time, ovarian weight, morphology and follicle count, as well as breeding and fertility were compared among groups. Only group IV was able to restore to normal body weight by the end of the observation period and resumed normal estrous cycles in a shorter time compared to other treatment groups. There was a decrease in primordial follicles in all treatment groups, but group III had the greatest reduction. Although, there was no difference in pregnancy, only one animal littered normal pups in group II, none littered in group III and four littered in group IV. Thus, cryopreservation and orthotopic transplantation of ovarian tissue can restore the fertility of rats subjected to chemotherapy in a manner that is superior to GnRHa treatment. We also observed increased rates of hepatic, splenic and pulmonary haemorrhage in group III, suggesting there may be synergistic toxicity of GnRHa and cyclophosphamide. © 2015 Li et al.


Yang Y.,Southwest Jiaotong University | Yang Y.,Anhui University of Traditional Chinese Medicine | Xia T.,452nd Hospital of Peoples Liberation Army | Chen F.,Southwest Jiaotong University | And 4 more authors.
Molecular Pharmaceutics | Year: 2012

Deep or chronic skin wounds are difficult to heal spontaneously due to the lack of scaffold to guide cell growth and reduced levels and activities of endogenous growth factors. Emulsion electrospinning process integrated with DNA condensation techniques indicated potentials to gradually release DNA, but no attempt has been made to clarify the advantages in promoting tissue regeneration and wound recovery. In this study, polyplexes of basic fibroblast growth factor-encoding plasmid (pbFGF) with poly(ethylene imine) were incorporated into electrospun fibers with a core-sheath structure, and poly(ethylene glycol) was included into the fiber sheath to allow a sustained release of pbFGF for 4 weeks. In vitro tests on mouse embryo fibroblasts indicated that pbFGF-loaded fibrous mats enhanced cell proliferation by the autocrine bFGF, and an effective cell transfection proceeded for over 28 days. Skin wounds were created in the dorsal area of diabetic rats for in vivo evaluation of skin regeneration after being covered with pbFGF-loaded fibrous mats. The gradual pbFGF release revealed significantly higher wound recovery rate with improved vascularization, enhanced collagen deposition and maturation, complete re-epithelialization and formation of skin appendages. The above results demonstrate the potential use of pbFGF-loaded electrospun fibrous mats to accelerate the healing of skin ulcers for patients with diabetic mellitus. © 2011 American Chemical Society.


Hou J.,Chengdu Military General Hospital | Zheng D.,71602 Medical Crop of Peoples Liberation Army | Zhong G.,452nd Hospital of Peoples Liberation Army | Hu Y.,Chengdu Military General Hospital
Canadian Journal of Physiology and Pharmacology | Year: 2013

The purpose of this study was to investigate the cardioprotective effect of mangiferin on diabetic cardiomyopathy (DCM). The DCM model was induced by a high-fat diet and a low dose of streptozotocin. We evaluated the characteristics of DCM by serial echocardiography, electron microscopy, histopathologic analysis of cardiomyocyte fibrosis area, and Western blot analysis of matrix metalloproteinase-2 (MMP-2) and MMP-9 expression. Rats with DCM showed severe left ventricular dysfunction and cardiac fibrosis. Mangiferin mitigated DCM and prevented the accumulation of myocardial collagen. These anatomic findings were accompanied by significant improvements in cardiac function. Based on these results, we conclude that mangiferin has a therapeutic effect on DCM and improves cardiac function.


Chen F.,Southwest Jiaotong University | Wan H.,Sichuan Provincial Peoples Hospital | Xia T.,452nd Hospital of Peoples Liberation Army | Guo X.,Southwest Jiaotong University | And 3 more authors.
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2013

Vascularization is one of the capital challenges in the establishment of tissue engineering constructs and recovery of ischemic and wounded tissues. The aim of this study was to assess electrospun fibers with loadings of multiple pDNA to allow a localized delivery for an efficient regeneration of mature blood vessels. To induce sufficient protein expression, a reverse microemulsion process was adopted to load pDNA into calcium phosphate nanoparticles (CP-pDNA), which were electrospun into fibers to achieve a sustained release for 4 weeks. Compared with pDNA-infiltrated fibers, the localized and gradual release of pDNA facilitated cell proliferation, gene transfection, and extracellular matrix secretion and enhanced the generation of blood vessels after subcutaneous implantation. Compared with commonly used pDNA polyplexes with poly(ethyleneimine), CP-pDNA nanoparticles induced significantly lower cytotoxicity and less inflammation reaction after implantation into animals. Fibers with encapsulated nanoparticles containing plasmids encoding vascular endothelial growth factor (pVEGF) and basic fibroblast growth factors (pbFGF) led to significantly higher density of mature blood vessels than those containing individual plasmid. It is suggested that the integration of CP-pDNA nanoparticles with loadings of multiple plasmids into fibrous scaffolds should provide clinical relevance for therapeutic vascularization, getting fully vascularized in engineered tissues and regeneration of blood vessel substitutes.


Li H.,Southwest Jiaotong University | Wan H.,Sichuan Provincial Peoples Hospital | Xia T.,452nd Hospital of Peoples Liberation Army | Chen M.,Southwest Jiaotong University | And 3 more authors.
Nanoscale | Year: 2015

Therapeutic angiogenesis remains the most effective method to re-establish a proper blood flow in ischemic tissues. There is a great clinical need to identify an injectable format to achieve a well accumulation following local administration and a sustained delivery of biological factors at the ischemic sites. In the current study, fragmented nanofibers with loaded traditional Chinese medicines, astragaloside IV (AT), the main active ingredient of astragalus, and ferulic acid (FA), the main ingredient of angelica, were proposed to promote the microvessel formation after intramuscular injection into ischemic hindlimbs. Fragmented fibers with average lengths of 5 (FF-5), 20 (FF-20) and 80 μm (FF-80) were constructed by the cryocutting of aligned electrospun fibers. Their dispersion in sodium alginate solution (0.2%) indicated good injectability. After injection into the quadriceps muscles of the hindlimbs, FF-20 and FF-80 fiber fragments showed higher tissue retentions than FF-5, and around 90% of the injected doses were determined after 7 days. On a hindlimb ischemia model established by ligating the femoral arteries, intramuscular injection of the mixtures of FA-loaded and AT-loaded FF-20 fiber fragments substantially reduced the muscle degeneration with minimal fibrosis formation, significantly enhanced the neovessel formation and hindlimb perfusion in the ischemic tissues, and efficiently promoted the limb salvage with few limb losses. Along with the easy manipulation and lower invasiveness for in vivo administration, fragmented fibers should become potential drug carriers for disease treatment, wound recovery and tissue repair after local injection. This journal is © The Royal Society of Chemistry.


Wang H.,Key Laboratory of Advanced Technologies of Materials | Wang H.,Southwest Jiaotong University | Zhang Y.,Key Laboratory of Advanced Technologies of Materials | Xia T.,452nd Hospital of Peoples Liberation Army | And 5 more authors.
Molecular Pharmaceutics | Year: 2013

The promotion of blood vessel initiation and growth plays an important role in the realization of therapeutic vascularization and regeneration of functional tissues. Astragalus membranaceus and angelica sinensis are commonly used traditional Chinese medicines for enriching the blood. In the current study astragaloside IV (AT, the main active ingredient of astragalus) and ferulic acid (FA, the main ingredient of angelica) were loaded into electrospun fibrous scaffolds to provide abundant and sustained biological factors required to initiate vascularization and bring it to maturity. The cell viability after AT and FA treatment was dose-dependent with an optimal concentration of around 50 μg/mL, and the most significant synergistic effect was demonstrated for the combined treatment with AT and FA with the ratio of 7/3 on both primary endothelial and smooth muscle cells. The in vitro release study showed that the amount of AT and FA release could be regulated by their loading amount and ratios in electrospun fibers. The localized and sustained codelivery of AT and FA indicated significantly high cell viability and secretion of extracellular matrices for both endothelial and smooth muscle cells, and induced significantly high densities of vascular structures after subcutaneous implantation. The most significant angiogenesis promotion with few inflammatory reactions was demonstrated for electrospun fibers containing AT and FA with the ratio of 7/3. It was suggested that the integration of the synergistic effect of Chinese medicine into electrospun fibrous scaffolds should provide clinical relevance for therapeutic vascularization, full vascularization in engineered tissues, and regeneration of blood vessel substitutes. © 2013 American Chemical Society.


He S.,Southwest Jiaotong University | Xia T.,452nd Hospital of Peoples Liberation Army | Wang H.,Southwest Jiaotong University | Wei L.,452nd Hospital of Peoples Liberation Army | And 2 more authors.
Acta Biomaterialia | Year: 2012

Key challenges associated with the outcomes of vascular grafting (for example, to fully vascularize engineered tissues and promptly regenerate blood vessel substitutes) remain unsolved. The local availability of angiogenic growth factors is highly desirable for tissue regeneration, and plasmid loading in scaffolds represents a powerful alternative for local production of tissue-inductive factors. No attempt has been made so far to clarify the efficacy of electrospun fibers with the loading of multiple plasmids to promote tissue regeneration. In the present study, core-sheath electrospun fibers with the encapsulation of polyplexes of basic fibroblast growth factor-encoding plasmid (pbFGF) and vascular endothelial growth factor-encoding plasmid (pVEGF) were evaluated to promote the generation of mature blood vessels. In vitro release indicated a sustained release of pDNA for ∼4 weeks with as low as ∼10% initial burst release, and the release patterns from the single and twofold plasmid-loaded systems coincided. In vitro investigations on human umbilical vein endothelial cells showed that the sustained release of pDNA from fibrous mats promoted cell attachment and viability, cell transfection and protein expression, and extracellular secretion of collagen IV and laminin. The acceleration of angiogenesis was assessed in vivo after subcutaneous implantation of fibrous scaffolds, and the explants were evaluated after 1, 2 and 4 weeks' treatment by histological and immunohistochemical staining. Compared with pDNA polyplex infiltrated fibrous mats, the pDNA polyplex encapsulated fibers alleviated the inflammation reaction and enhanced the generation of microvessels. Although there was no significant difference in the total number of microvessels, the density of mature vessels was significantly enhanced by the combined treatment with both pbFGF and pVEGF compared with those incorporating individual pDNA. The integration of the core-sheath structure, DNA condensation and multiple delivery strategies provided a potential platform for scaffold fabrication to regenerate functional tissues. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Guo X.,Southwest Jiaotong University | Xia T.,452nd Hospital of Peoples Liberation Army | Wang H.,Southwest Jiaotong University | Chen F.,Southwest Jiaotong University | And 3 more authors.
Pharmaceutical Research | Year: 2014

Purpose: The lack of control over microvasculature formation remains a key roadblock to the therapeutic vascularization and regeneration of functional tissues. In the current study, the integration of plasmid DNA (pDNA) condensation and electrospraying technologies was proposed to promote the regeneration of mature blood vessels through injectable or infusible administration of microparticles. Methods: Calcium phosphate (CP) nanoparticles with encapsulated plasmids encoding vascular endothelial growth factors (pVEGF) and basic fibroblast growth factor (pbFGF) were synthesized using reverse microemulsions. Electrosprayed microparticles with the loading of CP-pDNA nanoparticles were evaluated on both endothelial cells and smooth muscle cells and after subcutaneous infusion into animals. Results: CP-pDNA nanoparticles was obtained with an average size of around 110 nm and electrosprayed into microparticles, resulting in high loading efficiency and extended protection on pDNA from external DNase environment. The inoculation of poly(ethylene glycol) into microparticle matrices realized a gradual release for 4 weeks of CP-pDNA nanoparticles, leading to an incremental transfection efficiency and strong secretion of extracellular matrices. After subcutaneous infusion of microparticles with encapsulated both CP-pVEGF and CP-pbFGF nanoparticles, significantly higher densities of blood vessels were achieved than those containing individual nanoparticles, and induced a rapid generation of mature blood vessels with few cytotoxicity and inflammation reactions. Conclusions: Electrosprayed microparticle with CP-pDNA nanoparticles encapsulated promoted the formation of vascular networks, providing clinical relevance for therapeutic vascularization and regeneration of functional tissues after injection to ischemic sites or entrapment into tissue engineering scaffolds. © 2013 Springer Science+Business Media New York.


Xu Y.,452nd Hospital of Peoples Liberation Army | Luo S.,452nd Hospital of Peoples Liberation Army | Liu Y.,452nd Hospital of Peoples Liberation Army | Li J.,452nd Hospital of Peoples Liberation Army | And 8 more authors.
European Journal of Medical Research | Year: 2013

Background: Cancer is the result of a complex multistep process that involves the accumulation of sequential alterations of several genes, including those encoding microRNAs (miRNAs) that have critical roles in the regulation of gene expression.In this study, we aimed to predict potential mechanisms of bladder cancer related miRNAs and target genes by bioinformatics analyses. Methods. Here we used the method of text mining to identify nine miRNAs in bladder cancer and adopted protein-protein interaction analysis to identify interaction sites between these miRNAs and related-target genes. Results: There are two relationship types between bladder cancer and its related miRNAs: causal and unspecified. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment test showed that there were three pathways related to four miRNA targeted genes. The remaining five miRNAs annotated to disease are not enriched in the KEGG pathways. Of these, PIK3R1 is the overlapping gene among 38 genes in the cancer and bladder cancer pathways. Conclusions: These findings provide new insights into the role of miRNAs in the pathway of cancer and give us a hypothesis that miR-127 might play a similar role in regulation and control of PIK3R1. © 2013 Xu et al.; licensee BioMed Central Ltd.


PubMed | 452nd Hospital of Peoples Liberation Army
Type: Controlled Clinical Trial | Journal: Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2012

The aim of this study was to discuss the clinical effectiveness of high intensity focused ultrasound (HIFU) combined with gemcitabine administered by intra-arterial infusion on intermediate and advanced pancreatic cancer.Forty-eight patients with intermediate and advanced pancreatic cancer were divided into two groups. Twenty-four patients of the experimental group were treated by HIFU combined with gemcitabine, and 24 patients of the the HIFU group were treated by HIFU alone. Then the curative effect, extent of pain relief, and survival time were compared in the course of the treatment between the two groups.As compared with those in the control group, the overall response rate, level of pain relief, and 12-month survival rate after therapy were higher and the median survival time was longer in the joint group (P < 0.05).Ultrasound imaging, CT and associated tumor marker detection can make effective measurement to evaluate curative effect on pancreatic carcinoma. HIFU plus gemcitabine administered by intra-arterial infusion can improve the clinical therapeutic efficacy, pain relief, quality of life and long-term survival rate of patients with pancreatic cancer.

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