Fluorometric determination of acetamiprid using molecularly imprinted upconversion nanoparticles.

This paper describes the fabrication of an imprinted fluorescent nanoprobe based on SiO2-coated NaYF4: Yb, Er upconversion nanoparticles (UCNP) encapsulated with a molecularly imprinted polymer (MIP) for determination of acetamiprid. The fluorescent MIP nanoprobe was prepared using UCNP as the material for fluorescence signal readout, acetamiprid as template molecule, methylacrylic acid (MAA) as functional monomer, and ethyleneglycol dimethacrylate (EGDMA) as cross-linking agent. The molecular imprinting layers were immobilized on the surface of the UCNP@SiO2 by polymerization which occurred between the double bonds. UCNP@MIP shows a high selectivity towards acetamiprid with an imprinting factor (IF) of 7.84. When UCNP@MIP combines with acetamiprid, the fluorescence of the UCNP@MIP can be quenched due to the photo-induced electron transfer. Under optimum conditions, the fluorescence method shows a good linear relationship between the decreased fluorescence intensity (with excitation/emission peaks at 980/542 nm) and the variation of acetamiprid in the concentration range 20 to 800 ng mL-1. The limit of detection (LOD) is 8.3 ng mL-1. This fluorescence method was also successfully applied to detect acetamiprid in apple and strawberry samples. The recoveries range from 89.6 to 97.9%, with relative standard deviations between 1.6 and 2.9% (n = 5). Graphical abstractA simple fluorescence nanoprobe which integrates upconversion nanoparticles (UCNPs) and molecular imprinting polymer (MIP) was developed for the determination of acetamiprid. The limit of the detection was determined as 8.3 ng mL-1. The selectivity was enhanced by molecular imprinting, and the sensitivity was improved by the high sensitivity of the fluorescence emitted from the UCNPs.

A test strip for ochratoxin A based on the use of aptamer-modified fluorescence upconversion nanoparticles.

An aptamer-based test strip is described for visual and instrumental determination of the mycotoxin ochratoxin A (OTA). It is based on the use of NaYF4:Yb,Er upconversion nanoparticles (UCNPs) as a label for the aptamer and on the competition between OTA and its complementary sequence for an OTA-specific aptamer. To improve the analytical performance, the optical properties of the UCNPs, the fluidity of the UCNP-aptamer conjugate, and the migration rate on the nitrocellulose membranes were investigated. Under the optimal experimental conditions and by using a 980-nm laser, the relative fluorescence intensity (test line value/control line value) is proportional to the logarithm of the OTA concentration over a range from 5 to 100 ng·mL-1 (R2 = 0.9955). The limit of the detection is 1.86 ng·mL-1. This aptamer based flow assay can be performed within 15 min and has no serious cross-sensitivity to potentially interfering species. It was successfully applied to the determination of OTA in spiked wheat and beer samples. Graphical abstract An aptamer-based upconversion fluorescent strip based on the use of NaYF4:Yb,Er nanoparticles was developed for sensitive detection of Ochratoxin A. The limit of the detection was determined as 1.86 ng·mL-1. The assay can be performed within 15 min, indicating its great potential in point-of-care testing.

Complete Restoration of Hearing Loss and Cochlear Synaptopathy via Minimally Invasive, Single-Dose, and Controllable Middle Ear Delivery of Brain-Derived Neurotrophic Factor-Poly(dl-lactic acid-co-glycolic acid)-Loaded Hydrogel.

Noise-induced hearing loss (NIHL) often accompanies cochlear synaptopathy, which can be potentially reversed to restore hearing. However, there has been little success in achieving complete recovery of sensorineural deafness using nearly noninvasive middle ear drug delivery before. Here, we present a study demonstrating the efficacy of a middle ear delivery system employing brain-derived neurotrophic factor (BDNF)-poly-(dl-lactic acid-co-glycolic acid) (PLGA)-loaded hydrogel in reversing synaptopathy and restoring hearing function in a mouse model with NIHL. The mouse model achieved using the single noise exposure (NE, 115 dBL, 4 h) exhibited an average 20 dBL elevation of hearing thresholds with intact cochlear hair cells but a loss of ribbon synapses as the primary cause of hearing impairment. We developed a BDNF-PLGA-loaded thermosensitive hydrogel, which was administered via a single controllable injection into the tympanic cavity of noise-exposed mice, allowing its presence in the middle ear for a duration of 2 weeks. This intervention resulted in complete restoration of NIHL at frequencies of click, 4, 8, 16, and 32 kHz. Moreover, the cochlear ribbon synapses exhibited significant recovery, whereas other cochlear components (hair cells and auditory nerves) remained unchanged. Additionally, the cochlea of NE treated mice revealed activation of tropomyosin receptor kinase B (TRKB) signaling upon exposure to BDNF. These findings demonstrate a controllable and minimally invasive therapeutic approach that utilizes a BDNF-PLGA-loaded hydrogel to restore NIHL by specifically repairing cochlear synaptopathy. This tailored middle ear delivery system holds great promise for achieving ideal clinical outcomes in the treatment of NIHL and cochlear synaptopathy.

A Biodegradable, Adhesive, and Stretchable Hydrogel and Potential Applications for Allergic Rhinitis and Epistaxis.

Bioadhesive hydrogels have attracted considerable attention as innovative materials in medical interventions and human-machine interface engineering. Despite significant advances in their application, it remains critical to develop adhesive hydrogels that meet the requirements for biocompatibility, biodegradability, long-term strong adhesion, and efficient drug delivery vehicles in moist conditions. A biocompatible, biodegradable, soft, and stretchable hydrogel made from a combination of a biopolymer (unmodified natural gelatin) and stretchable biodegradable poly(ethylene glycol) diacrylate is proposed to achieve durable and tough adhesion and explore its use for convenient and effective intranasal hemostasis and drug administration. Desirable hemostasis efficacy and enhanced therapeutic outcomes for allergic rhinitis are accomplished. Biodegradation enables the spontaneous removal of materials without causing secondary damage and minimizes medical waste. Preliminary trials on human subjects provide an essential foundation for practical applications. This work elucidates material strategies for biodegradable adhesive hydrogels, which are critical to achieving robust material interfaces and advanced drug delivery platforms for novel clinical treatments.

In vitro evaluation of tobramycin and aztreonam versus Pseudomonas aeruginosa biofilms on cystic fibrosis-derived human airway epithelial cells.

OBJECTIVES: Aztreonam for inhalation solution (AZLI) was recently approved by the FDA for treating cystic fibrosis (CF) patients infected with Pseudomonas aeruginosa. Here we investigated the effect of aztreonam alone or in combination with tobramycin on P. aeruginosa biofilms grown on CF airway epithelial cells. METHODS: P. aeruginosa biofilms, produced by laboratory strains or clinical isolates, were formed on confluent CF airway cells before treatment overnight with aztreonam or tobramycin alone or in combination. Alternatively, antibiotics were added 1 h after bacterial inoculation to assess their ability to impair biofilm formation at 5 h. Bacterial cfu remaining after treatment were then determined by plate counting. RESULTS: In the absence of antibiotics, all strains developed biofilms that disrupted CF airway epithelial monolayers overnight. Tobramycin reduced the cfu of all strains grown as biofilms. Aztreonam reduced the cfu of some strains by ∼1 log unit without preserving the integrity of cystic fibrosis airway cell monolayers, while decreasing the biofilms of other clinical isolates by ∼4 log units and protecting the monolayers from being compromised. The combination of aztreonam and tobramycin reduced the cfu of two strains by an additional 0.5 and 2 log units, respectively. Of all the mechanisms explored, Psl exopolysaccharide production might explain the variations in biofilm tolerance to aztreonam in some of the strains. CONCLUSIONS: Effects of aztreonam on P. aeruginosa biofilms in the in vitro co-culture model are strain-dependent. The simultaneous application of aztreonam and tobramycin may be beneficial for a subset of CF patients by eliminating susceptible P. aeruginosa strains.

Discrimination of vestibular function based on inertial sensors.

BACKGROUND AND OBJECTIVE: Vestibular dysfunction, as a common disease or symptom, can cause abnormalities in gait and balance. Since the existing detection methods are static detection and cannot obtain the dynamic vestibular information of patients, this paper proposes a simple method for detecting vestibular dysfunction based on gait signals of subjects. METHODS: In our study, the walking patterns of dynamic gait index (DGI) and inertial sensor were adopted for the data acquisition. Time-domain, frequency-domain and non-linear features were extracted from inertial sensor signals. Then the Relief algorithm was used for feature selection. Two classifiers, Support Vector Machine (SVM) and Random Forest (RF), were used to classify the patients with vestibular dysfunction and the healthy controls. RESULTS: The highest accuracy of 84.79% was achieved based on magnetometer features and SVM classifier. To further improve classification results, features of three sensor signals were combined and applied to two classifiers. Combined features and RF classifier achieved a classification accuracy of 86.5%. CONCLUSION: The detection of vestibular dysfunction based on inertial sensors might be simple, accurate and easy to implement in clinical examination, which provides a new method for the clinical diagnosis of vestibular function.

Pseudomonas aeruginosa PAO1 Is Attracted to Bovine Bile in a Novel, Cystic Fibrosis-Derived Bronchial Epithelial Cell Model.

Cystic fibrosis (CF) is a life-threatening, inherited, multi-organ disease that renders patients susceptible throughout their lives to chronic and ultimately deteriorating protracted pulmonary infections. Those infections are dominated in adulthood by the opportunistic pathogen, Pseudomonas aeruginosa (Pa). As with other advancing respiratory illnesses, people with CF (pwCF) also frequently suffer from gastroesophageal reflux disease (GERD), including bile aspiration into the lung. GERD is a major co-morbidity factor in pwCF, with a reported prevalence of 35-81% in affected individuals. Bile is associated with the early acquisition of Pa in CF patients and in vitro studies show that it causes Pa to adopt a chronic lifestyle. We hypothesized that Pa is chemoattracted to bile in the lung environment. To evaluate, we developed a novel chemotaxis experimental system mimicking the lung environment using CF-derived bronchial epithelial (CFBE) cells which allowed for the evaluation of Pa (strain PAO1) chemotaxis in a physiological scenario superior to the standard in vitro systems. We performed qualitative and quantitative chemotaxis tests using this new experimental system, and microcapillary assays to demonstrate that bovine bile is a chemoattractant for Pa and is positively correlated with bile concentration. These results further buttress the hypothesis that bile likely contributes to the colonization and pathogenesis of Pa in the lung, particularly in pwCF.

Comparison and evaluation of three techniques for treating auricular pseudocyst.

BACKGROUND: Auricular pseudocyst is a benign cystic lesion in cartilages of the auricle. Different methods are currently used to manage this disease. In these methods, simple aspiration combined with pressure dressing, local steroid injection and surgery are the most prevalent therapies. OBJECTIVE: To find the best clinical path for the treatment of auricular pseudocyst. METHODS: Eighty-four subjects were randomly allocated into three equal groups (Group A: simple suction combined with pressure dressing; Group B: suction and local steroid injection; and, Group C: surgery). Two otolaryngologists assessed effective rate, sequelae and degree of satisfaction at three-month follow-up. A visual analog scale was used to determine degree of satisfaction. RESULTS: Group A had the lowest effective rate (54%). Group C was highest in terms of effectiveness (100%) but also in incidence of sequelae (71%). Group B had a slightly lower effective rate (86%) than Group C, but the incidence of sequelae was lowest (42%). Degree of satisfaction was highest (7.0 ± 2.7) for Group B. CONCLUSION: Local steroid injection should be the first choice for the treatment of auricular pseudocyst because of high satisfaction, favorable effectiveness and few sequelae. Where this method is ineffective, surgery should be used.

A New Case of Endoscopic Resection of a Chorda Tympani Schwannoma.

Chorda tympani schwannoma is a very rare tumor, with only 12 reported cases in the English literature. There are few reports on the diagnosis of chorda tympani schwannoma, and it is easily misdiagnosed. At present, surgery is recognized as a treatment for chorda tympani schwannoma. We describe the clinical course of a patient presenting with a chorda tympani schwannoma treated with surgical resection using a transcanal endoscopic approach, and the results after this treatment were satisfactory. Therefore, we accordingly advocate the minimally invasive method of transcanal endoscopic resection to maximize intraoperative visualization and reduce postoperative morbidity for middle ear tumors.

Cochlear resident macrophage mediates development of ribbon synapses via CX3CR1/CX3CL1 axis.

Cochlear ribbon synapses formed between spiral ganglion neurons and inner hair cells in postnatal mice must undergo significant morphological and functional development to reach auditory maturation. However, the mechanisms underlying cochlear ribbon synapse remodeling remain unclear. This study found that cochlear resident macrophages are essential for cochlear ribbon synapse development and maturation in mice via the CX3CR1/CX3CL1 axis. CX3CR1 expression (a macrophage surface-specific receptor) and macrophage count in the cochlea were significantly increased from postnatal day 7 then decreased from days 14 to 28. Seven-day treatment with CX3CR1 inhibitors and artificial upregulation of CX3CL1 levels in the inner ear environment using the semicircular canal injection technique were initiated on day 7, and this resulted in a significant increase in hearing threshold on day 28. Additionally, abnormalities in the morphology and number of cochlear ribbon synapses were detected on day P14, which may be associated with hearing impairment. In conclusion, macrophage regulation of cochlear ribbon synapse remodeling via the CX3CR1/CX3CL1 axis is required during hearing development and offers a new perspective on immune-related hearing loss throughout auditory development. Importantly, it could be a new treatment target for sensorineural hearing loss.

Live-Cell Imaging Shows Uneven Segregation of Extrachromosomal DNA Elements and Transcriptionally Active Extrachromosomal DNA Hubs in Cancer.

Oncogenic extrachromosomal DNA elements (ecDNA) play an important role in tumor evolution, but our understanding of ecDNA biology is limited. We determined the distribution of single-cell ecDNA copy number across patient tissues and cell line models and observed how cell-to-cell ecDNA frequency varies greatly. The exceptional intratumoral heterogeneity of ecDNA suggested ecDNA-specific replication and propagation mechanisms. To evaluate the transfer of ecDNA genetic material from parental to offspring cells during mitosis, we established the CRISPR-based ecTag method. ecTag leverages ecDNA-specific breakpoint sequences to tag ecDNA with fluorescent markers in living cells. Applying ecTag during mitosis revealed disjointed ecDNA inheritance patterns, enabling rapid ecDNA accumulation in individual cells. After mitosis, ecDNAs clustered into ecDNA hubs, and ecDNA hubs colocalized with RNA polymerase II, promoting transcription of cargo oncogenes. Our observations provide direct evidence for uneven segregation of ecDNA and shed new light on mechanisms through which ecDNAs contribute to oncogenesis. SIGNIFICANCE: ecDNAs are vehicles for oncogene amplification. The circular nature of ecDNA affords unique properties, such as mobility and ecDNA-specific replication and segregation behavior. We uncovered fundamental ecDNA properties by tracking ecDNAs in live cells, highlighting uneven and random segregation and ecDNA hubs that drive cargo gene transcription.See related commentary by Henssen, p. 293.This article is highlighted in the In This Issue feature, p. 275.

Integrating supply and demand factors for estimating ecosystem services scarcity value and its response to urbanization in typical mountainous and hilly regions of south China.

In the process of rapid urbanization, the decline in ecosystems' physical supply value is a direct result of the increasing demands of human development. The ecosystem services value combined with supply and demand factors can be used to obtain the ecosystem services scarcity value (ESSV). These ecosystems with larger ESSVs warrant increased protection, or at the very least a development plan to ensure a balance between their continued existence and human usage. However, urbanization and other developmental effects have often caused the ESSV of those regions to be disregarded, which produces an imbalance in the ecosystem. This paper evaluated the spatial differentiation of ESSV based on heterogeneous units in the Yuebei region, China. Then, a spatial response analysis of the ESSV to urbanization according to the spatial correlation model and Getis-Ord Gi* was conducted. The results showed that the ecosystem service physical supply value declined due to urban sprawl in 1990-2015, but the ESSV increased sharply during the same time with its acceleration being particularly strong after 2000. Areas with higher ESSV were concentrated in the northern region due to a higher prevalence of woodland. Urbanization accelerated significantly after 2000, and it is found that similar tendencies of ESSV and urbanization occurred over the same period. Surprisingly, the ESSV was negatively correlated with urbanization in local regions, and their interaction continued to increase over time. The spatial hotspot map of the ESSV and urbanization also formed an opposite pattern. In addition, the grid number of High-Low and Low-High types is more than half of the total number of aggregated grids. According to the results, understanding the variation in the ESSV clearly due to urbanization and identifying their interaction in local regions can provide a more specific direction for future resource adjustment and ecosystem service improvements.

Double-enzymes-mediated fluorescent assay for sensitive determination of organophosphorus pesticides based on the quenching of upconversion nanoparticles by Fe3.

Herein, a new double-enzymes-modulated fluorescent assay based on the quenching of upconversion nanoparticles (UCNPs) by Fe3+ was constructed for sensitive determination of OPs. OPs can inhibit the activity of acetylcholinesterase to reduce the production of choline and further lead to the lack of H2O2 in the presence of choline oxidase. Therefore, Fe2+ cannot be converted into Fe3+, resulting in "turn-on" fluorescence of UCNPs. Under optimal conditions, an excellent linear correlation between the inhibition efficiency and the logarithm of the chlorpyrifos concentration was achieved with a detection limit (LOD) of 6.7 ng/mL in the range of 20-2000 ng/mL. The recovery for chlorpyrifos in apples and cucumbers was 89.5-97.1%. The results were consistent with those obtained by GC-MS. Overall, the integration of UCNPs into the double-enzymes-mediated Fe3+/Fe2+ conversion endows this method with desirable rapidity, sensitivity, selectivity, stability, operational simplicity, and strong anti-interference capability, holding great potential in the application of food safety.

Colorimetric aptasensor for the detection of mercury based on signal intensification by rolling circle amplification.

Techniques that are sensitive to detect mercury ion (Hg2+) are very important, due to its serious threat to public health and food security. In this work, a colorimetric aptasensor was fabricated for the detection of Hg2+ based on rolling circle amplification (RCA). The aptamer was immobilized onto the microplate and hybridized with its complementary strand (cDNA1) which linked with a primer for triggering the RCA reaction of circular template. The successfully RCA process led to the formation of long ssDNA chains on the microplate, which created many hybridized DNA fragments for bio-cDNA2. The tagged amount of horseradish peroxidase (HRP) was enhanced through the avidin/biotin binding between avi-HRP and bio-cDNA2. In the addition of TMB-H2O2, HRP was catalyzed and generated an optical signal. However, in the presence of target, Hg2+ specifically and preferentially bound with aptamer and formed a strong and stable T-Hg2+-T complex, which led to the release of cDNA1 and HRP cluster. Consequently, the optical signal decreased. Our results showed that the limit of detection (LOD) of this system was 1.6 nM with excellent specificity, and that the detection signals were enhanced by up to 18 times under RCA conditions when compared with detections without RCA. This method has been successfully used to detect Hg2+ in water samples with a recovery of 98%-105.74%.

Quantifying the Impact of the Grain-for-Green Program on Ecosystem Health in the Typical Agro-Pastoral Ecotone: A Case Study in the Xilin Gol League, Inner Mongolia.

The Green-for-Grain program (GGP) is the largest environmental restoration program in China. It is effective in controlling land desertification but at the same time is highly affected by regional differences. Ecosystem health, as an important indicator of ecosystem sustainability, can effectively assess the ecological impact of the GGP and provide a basis for follow-up actions. As a typical agro-pastoral ecotone along the Great Wall, the Xilin Gol League has seen increasing land-use intensity, thus, it is crucial to understand the ecological conditions of the region in order to deploy a policy of the GGP in accordance with local conditions. In this study, using remote sensing images and social statistics data from 1990-2015, land-use transformation and the turning point of vegetation coverage was determined. Based on the pressure-state-response (PSR) model, an ecological health evaluation system was constructed to quantify the temporal and spatial variation of ecosystem health. Then, the spatial correlation between the changes in forest and grass coverage, as well as the changes in the ecosystem health index (EHI), was evaluated using GeoDa software. The results showed that (1) grassland was the primary land-use/land-cover (LULC) in the Xilin Gol League. Since 2000, land-use transfer types changed significantly and grassland degradation weakened; landscape connectivity increased, and vegetation coverage increased. (2) Over the past 25 years, the ecosystem in the study area was at a subhealthy level and showed a trend toward a healthy level. (3) The spatial correlation between △Area% (change in forest and grass coverage) and △EHI (change in ecosystem health index) was positive between 2000 and 2015 and the correlation gradually increased, indicating that the GGP did enhance the health of the ecosystem of Xilin Gol. This study provided a specific reference for the evaluation of ecosystem health in the agro-pastoral ecotone of China and a theoretical basis for the implementation of sustainable management policies in the study area.

Reliability, internal consistency, and concurrent validity of a modified version of the dynamic gait index in people with vestibular disorders.

BACKGROUND: People with vestibular disorders often have abnormalities in gait and balance. The Dynamic Gait Index (DGI) is a relatively effective clinical gait measure that has been validated for use in patients with vestibular disorders. The modified version of the DGI (M-DGI) is based on the original DGI. RESEARCH QUESTION: The objective of this study was to refine and test the clinical application of the M-DGI, and to investigate whether it is an effective indicator of dynamic gait in patients with vestibular disorders. METHODS: A reliability and validity study. All raters reviewed the instructions and scoring criteria for each M-DGI item prior to the initial test. The raters simultaneously scored two M-DGI tasks for the 75 subjects, and the two tasks were completed with an interval of two hours in-between. Reliability of total M-DGI scores was assessed using intraclass correlation coefficients (2,1). Internal consistency of the M-DGI was evaluated using Cronbach's alpha. Concurrent validity of the M-DGI with Dizziness Handicap Inventory (DHI) and Timed "Up & Go" Test (TUG) was assessed using Spearman's rank order correlation coefficient. RESULTS AND SIGNIFICANCE: Interrater and intrarater reliability of the total M-DGI scores were reflected by ICCs of 0.99 and 0.97. Internal consistency of the M-DGI score was 0.9975. Spearman's rank order correlation coefficient of the M-DGI score with the Dizziness Handicap Inventory (DHI) and the Timed "Up & Go" Test (TUG) was 0.72 and 0.65, respectively.The M-DGI demonstrates acceptable reliability, internal consistency, and concurrent validity for use as a clinical gait measurement for patients with vestibular disorders.

Pseudo-Benign Paroxysmal Positional Vertigo: A Retrospective Study and Case Report.

Pseudo-benign paroxysmal positional vertigo (pseudo-BPPV) is a specific type of vestibular migraine disguised as benign paroxysmal positional vertigo, which is characterized by recurrent different types of positional and atypical positional vertigo with migraine features. It is easy to be misdiagnosed with BPPV at the first visit, which means that the ideal therapeutic effects are not achieved. Twenty-five cases of pseudo-BPPV with frequent changing positional vertigo were retrospected and the following key features help to identify the disease: recurrent positional and atypical positional vertigo, migrainous accompanying symptoms or migraine history, mild or indistinctive headaches, with or without impaired vestibular function, ineffective for simply reposition. And we found that vertigo in pseudo-BPPV can be preferable controlled by valproic acid combined with canalith repositioning procedure.

Surface-enhanced Raman spectroscopic-based aptasensor for Shigella sonnei using a dual-functional metal complex-ligated gold nanoparticles dimer.

Herein, we constructed an aptamer-based sensor for the sensitive and highly specific detection of Shigella sonnei via surface enhanced Raman spectroscopy (SERS) analysis. A composite material integrated of the Raman active 4-MBA ligand of the Eu-complex and citrate-stabilized Au nanoparticles (cit-Au NPs) was synthesized and served as both active substrate and Raman reporter. Aptamers targeted to S. Sonnei was then modified onto the surface of this dual-functional material. With the introduction of S. Sonnei, aptamer bound with target with high affinity and specificity, leaving the dual-functional material onto the bacteria. The SERS intensity response showed a strong positive linear correlation (R = 0.9956) with increasing concentrations of S. sonnei (ranging from 10 to 106 cfu/mL). High specificity was achieved at Shigella species (S. dysenteriae, S. flexneri, S. boydii) and other common bacteria (Salmonella typhimurium, Staphylococcus aureus and Escherichia coli). When applied in real samples, the approach showed recoveries from 92.6 to 103.8 %. The designed approach holds great potential for the construction of various aptasensors for the effective and convenient detection of different food hazards.

Multi-functional self-assembled nanoparticles for pVEGF-shRNA loading and anti-tumor targeted therapy.

Although RNA interference (RNAi) technology shows great potential in cancer treatment, the tumor target delivery and sufficient cytosolic transport of RNAi agents are still the main obstacles for its clinical applications. Herein, we report a functional supramolecular self-assembled nanoparticle vector for RNAi agent loading and tumor target therapy. Molecular block adamantane-grafted poly(ethylene glycol) (Ad-PEG) was modified with epidermal growth factor receptor (EGFR)-specific binding ligand GE11 or pH-sensitive fusogenic peptide GALA and then used for self-assembly with cyclodextrin-grafted branched polyethylenimine (CD-PEI), adamantane-grafted polyamidoamine dendrimer (Ad-PAMAM), and plasmid DNA containing a small hairpin RNA expression cassette against vascular endothelial growth factor (VEGF) into functional DNA-loaded supramolecular nanoparticles (GE11&GALA-pshVEGF@SNPs) based on molecular recognition and charge interaction. These functional peptides facilitated the target cell binding, internalization, and endosomal escape of GE11&GALA-pshVEGF@SNPs, resulting in increased reporter gene expression and efficient targeted gene silencing. The systemic delivery of the GE11&GALA-pshVEGF@SNPs can efficiently downregulate the intratumoral VEGF protein levels, reduce blood vessel formation, and significantly inhibit A549 xenograft tumor growth. These results reveal the potential of these multifunctional self-assembled nanoparticles as a nucleic acid drug delivery system for the treatment of lung cancer.

Efficacy and safety of cinobufacini injection combined with vinorelbine and cisplatin regimen chemotherapy for stage III/IV non-small cell lung cancer: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The main component of cinobufacini injection is dry toad skin, which is used as adjuvant therapy for stage III/IV non-small cell lung cancer patients in long-term combination with vinorelbine and cisplatin. However, the efficacy and safety of this combination therapy remain unclear. METHODS: A systematic review and meta-analysis will be conducted following the preferred reported items for systematic review and meta-analysis guidelines. Two independent reviewers (LRL and ZLN) will carry out a comprehensive search of the PubMed, Web of Science, Cochrane Library, EMBASE, the Chinese Science and Technology Periodical Database, China National Knowledge Infrastructure, Wanfang Databases, China Biology Medicine. The last search date will be July 30, 2020. Reference list of all selected articles will independently screened to identify additional studies left out in the initial search. The Cochrane Risk of Bias Tool will be used to evaluate the risk of bias of the randomized controlled trials. Outcome index: The main efficacy indicators were based on the objective efficacy evaluation criteria of the World Health Organization antineoplastic drugs or the objective efficacy evaluation criteria of solid tumors established by RECIST. Secondary criteria Karnofsky performance scale (KPS) score, pain efficacy criteria, side effects of chemotherapy such as myelosuppression and gastrointestinal symptoms. Assessment of risk of bias and data synthesis will be conducted using Review Manager V5.3 software. RESULTS: This study will systematically evaluate the efficacy and safety of cinobufacini combined with vinorelbine and cisplatin in the treatment of stage III/IV non-small cell lung cancer. The results of this systematic review will be published in peer-reviewed scientific journals. ETHICS: The ethical approval is not required since systematic review is based on published studies. INPLASY REGISTRATION NUMBER: INPLASY202060091.