Synthetic genomic nanomedicine with triple-responsiveness for systemic anti-tumor therapy.

To overcome the biological barriers in the journey of systemic gene delivery, a multifaceted genomic synthetic nanomedicine was elaborated and strategically equipped with a multiple of intriguing responsiveness. Particularly, core-shell plasmid DNA condensates were created based on polyionic complexation with block copolymer of polyethylene glycol (PEG)-polylysine (PLys), namely, the nanoscaled PLys&pDNA nanoparticle tethered with the biocompatible PEG surroundings. Furthermore, redox-reversible disulfide crosslinking was introduced into PLys&pDNA nanoparticle to accomplish adequate structural stabilities, and thermal-responsive polypropylacrylamide (PNIPAM) was introduced as the secondary intermediate surroundings onto the pre-formulated PLys&pDNA nanoparticle with the aim of preventing the potential enzymatic degradation from the environmental nucleases. Hence, hundreds of times prolonged survival and retention was determined in pertinent to the blood circulation properties. Additionally, the installation of a guide ligand at the distal end of PEG segments was proposed to encourage selective tumor uptake. A linear peptide of GPLGVRG, which is selectively susceptible to digestion by the tumor-enriched matrix metalloproteinase 2 (MMP-2), was used as the linkage between the shell and core. This peptide has been shown to detach the bio-inert PEGylation, resulting in further facilitated cell endocytosis and intracellular trafficking activities. Hence, the precisely defined synthetic nanomedicine, which exhibits desirable characteristics, efficient expression of the therapeutic gene in the affected cells, and contributed to potent therapeutic efficacy in systemic treatment of intractable tumors by encapsulating the anti-angiogenic gene.

Efficacy of Chinese and Western Medical Techniques in Treating Diabetic Foot Ulcers With Necrotizing Fasciitis of the Lower Leg.

To analyze and evaluate the clinical efficacy of Chinese and Western medical techniques in the treatment of severe diabetic foot ulcers complicated with necrotizing fasciitis of the lower leg and summarize the treatment experience of such patients to identify a new method of limb salvage treatment. A total of 46 patients with severe diabetic foot ulcers and necrotizing fasciitis of the lower leg were treated with such techniques as surgical debridement, bone drilling, open joint fusion, and microskin implantation. Wounds were treated with moisture-exposed burn therapy (a regenerative medical treatment for burns, wounds, and ulcers) and moisture-exposed burn ointment (a traditional Chinese medicine); underlying diseases were also treated effectively. The wound healing time, rate of high amputation, and mortality of these patients were summarized, and the clinical efficacy of such treatments was evaluated. Of the 46 patients enrolled, 38 patients were cured, with a cure rate of 82.61%. The average wound healing time was 130 ± 74.37 days. Two patients underwent high amputations, with an amputation rate of 4.35%, and 4 deaths occurred, with a mortality rate of 8.70%. The combination of Chinese and Western medical techniques in the treatment of severe diabetic foot ulcers complicated with necrotizing fasciitis of the lower leg not only effectively saved patients' lives and promoted wound healing but also greatly reduced the rates of high amputation and disability.

Multi-stage surgery combined with radiotherapy for treatment of giant anterior chest wall keloid: A case report.

RATIONALE: Giant keloids often have indications for surgical resection, but postoperative reconstruction of the skin and high recurrence of keloids are a challenge for clinical treatment. This article reports a rare successful treatment of a giant keloid in the anterior chest wall by multistage surgery combined with radiotherapy, which is why this case is meaningful. PATIENT CONCERNS: A 66-year-old woman presented a giant keloid with ulcerations and severe itching on the anterior chest wall. She had a history of keloid disease for more than 10 years, and had been treated by multiple operations, with no success. DIAGNOSES: The patient was diagnosed as keloid based on her history and symptoms. Histopathology findings supported our diagnosis. INTERVENTIONS: We successfully excised the keloid after 5 operations and 2 rounds of electron-beam radiotherapy, which was applied at 24 hours after the 4th and 5th operation. OUTCOMES: There was no sign of recurrence over the follow-up period of 24 months. LESSONS: The combination of multistage surgery and radiotherapy presents as a good choice for the treatment of giant keloids.

Low evolutionary risk of iprovalicarb resistance in Phytophthora infestans.

Iprovalicarb is a carboxylic acid amide (CAA) fungicide, highly effective in the control of potato late blight, causing by Phytophthora infestans. Due to cross-resistance with other CAA fungicides and moderate resistance risk of P. capsici to iprovalicarb, the evolutionary risk of P. infestans resistance to this fungicide and the contribution of inherited genes and environmental effect was evaluated using a common garden experiment. The results showed that the ratio of heritability and plasticity of iprovalicarb in the seven populations equaled 1.0, indicating both inherited genes and environmental factors were essential to iprovalicarb sensitivity in P. infestans. The pairwise population differentiation determined by SSR loci (FST) between populations ranged from 0.007 to 0.133 and the overall FST was significantly higher than population differentiation in RGR (QST), suggesting constraining selection acting on iprovalicarb sensitivity. We also found a new indicator of growth rate inhibition (GRI) for fungicide sensitivity, which was negatively correlated to growth rate in the absence of iprovalicarb, indicating a trade-off between iprovalicarb resistance and pathogen's growth. The constraining selection plus a trade-off between GRI and growth rate revealed low risk of P. infestans evolving resistance to iprovalicarb.

Comparative analyses of fungicide sensitivity and SSR marker variations indicate a low risk of developing azoxystrobin resistance in Phytophthora infestans.

Knowledge of the evolution of fungicide resistance is important in securing sustainable disease management in agricultural systems. In this study, we analyzed and compared the spatial distribution of genetic variation in azoxystrobin sensitivity and SSR markers in 140 Phytophthora infestans isolates sampled from seven geographic locations in China. Sensitivity to azoxystrobin and its genetic variation in the pathogen populations was measured by the relative growth rate (RGR) at four fungicide concentrations and determination of the effective concentration for 50% inhibition (EC50). We found that all isolates in the current study were sensitive to azoxystrobin and their EC50 was similar to that detected from a European population about 20 years ago, suggesting the risk of developing azoxystrobin resistance in P. infestans populations is low. Further analyses indicate that reduced genetic variation and high fitness cost in resistant mutations are the likely causes for the low evolutionary likelihood of developing azoxystrobin resistance in the pathogen. We also found a negative correlation between azoxystrobin tolerance in P. infestans populations and the mean annual temperature of collection sites, suggesting that global warming may increase the efficiency of using the fungicide to control the late blight.

Limited Sexual Reproduction and Quick Turnover in the Population Genetic Structure of Phytophthora infestans in Fujian, China.

The mating system plays an important role in the spatiotemporal dynamics of pathogen populations through both its direct and indirect impact on the generation and distribution of genetic variation. Here, we used a combination of microsatellite and phenotypic markers to investigate the spatiotemporal distribution of genetic variation in Phytophthora infestans isolates collected from Fujian, China and to determine the role of sexual reproduction in the dynamics. Although the pathogen populations in this region were dominated by self-fertile genotypes, sexual reproduction only occurred occasionally and its contributions to the population genetic structure of P. infestans and epidemics of late blight in the region were limited. Only 49 genotypes were detected among the 534 isolates assayed and the pathogen populations displayed significant heterozygosity excess. Hierarchical analysis revealed that 21.42% of genetic variation was attributed to the difference among sampling years while only 4.45% was attributed to the difference among locations, suggesting temporal factors play a more important role in the population genetic dynamics of P. infestans than spatial factors in this region. We propose that clonal reproduction, combined with founder effects and long distance dispersal of sporangia, is responsible for the observed pattern of spatiotemporal dynamics in P. infestans.