Regenerative Flexible Upconversion-Luminescence Biosensor for Visual Detection of Diethylstilbestrol Based on Smartphone Imaging.

Diethylstilbestrol (DES), an endocrine disrupting chemical, has been linked to serious health problems in humans. In this work, a regenerative flexible upconversion-fluorescence biosensor was designed for the detection of DES in foodstuffs and environmental samples. Herein, amino-functionalized upconversion nanoparticles (UCNPs) were synthesized and immobilized on the surface of a flexible polydimethylsiloxane substrate, which was further modified with complementary DNA and dabcyl-labeled DES aptamer. The fluorescence resonance energy transfer (FRET) system was established for DES detection between dabcyl and UCNPs as the acceptor and donor pairs, respectively, which resulted in the quenching of the upconversion luminescence intensity. In the presence of a target, the FRET system was destroyed and upconversion fluorescence was restored due to the stronger affinity of the aptamer toward DES. The designed biosensor was also implemented in a dual-mode signal readout based on images from a smartphone and spectra from a spectrometer. Under the optimized experimental conditions, good linear relationships were achieved based on imaging (y = 53.055x + 36.175, R2 = 0.9851) and spectral data (y = 1.1582x + 1.9561, R2 = 0.9897). The designed biosensor revealed great practicability with a spiked recovery rate of 77.91-97.95% for DES detection in real environment and foodstuff samples. Furthermore, the proposed biosensor was regenerated seven times with an accuracy threshold of 80% demonstrating its durability and reusability. Thus, this biosensor is expected to be applied to point-of-care and on-site detection based on the developed portable smartphone device and android application.

Knowledge, attitude, and practice of medication among Haikou residents.

BACKGROUND: Our study aims to explore the knowledge, attitude, and practice (KAP) and its influencing factors of medication among residents in Haikou, the capital city of Hainan Province, and inform the development of interventions to reduce residents' medication errors. METHODS: A cross-sectional questionnaire survey was conducted to investigate the KAP of medication among Haikou residents and its influencing factors from March to September 2019. RESULTS: A total of 471 valid questionnaires were collected (245 online and 226 offline), with an effective recovery rate of 94.2%. The average score of KAP of medication were 52.2±13.08, 27.34±8.14, and 51.54±9.22, respectively. The knowledge score reached "good" in the evaluation criteria of the questionnaire, and the attitude and practice scores were "fair". Multiple linear regression analysis revealed the medication knowledge increased with age; a lower education degree was associated with less knowledge and more medication errors, and a higher education level was associated with more access to medication knowledge. CONCLUSIONS: Education on rational drug use should be performed via multiple ways to promote rational drug use and reduce risky medication behaviors, particularly among residents with low education degrees, e.g., drug counseling and guidance, regularly push medication science popularization, public welfare lecture on rational drug use, organize and compile popular science books.

Tentative identification of gefitinib metabolites in non-small-cell lung cancer patient plasma using ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass spectrometry.

BACKGROUND: Gefitinib is an orally potent and selective ATP-competitive inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase and is commonly used to treat locally advanced or metastatic non-small-cell lung cancer (NSCLC) with sensitive EGFR mutations. Multiple adverse effects associated with gefitinib, including liver and lung injuries, severe nausea, and diarrhea, have limited its clinical application. Xenobiotic-induced bioactivation is thought to be an important reason for gefitinib toxicity, which encouraged us to clarify the metabolism of gefitinib in NSCLC patients. MATERIALS AND METHODS: An ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass spectrometry (UPLCQ-TOF-MS) method was established to tentatively identify the metabolites of gefitinib in human plasma. The extracted ion chromatogram peak intensity threshold was set at 1500 cps with minimum MS and MS/MS peak intensities of 400 and 100 cps, respectively. RESULTS: A total of 18 tentative metabolites were identified. Eight novel tentative metabolites with metabolic changes in dechlorination, defluorination, and hydrogenation on the quinazoline skeleton; removal of a partial or complete 3-chloro-4-fluoroaniline-substituted group; and sulfate conjugation and taurine conjugation were newly discovered in human plasma. Based on structural analysis of the tentative metabolites, the metabolic pathways were proposed. In addition, the pathways of dechlorination, defluorination, and hydrogenation on the quinazoline skeleton; removal of partial or complete 3-chloro-4-fluoroaniline-substituted groups; and sulfate conjugation and taurine conjugation in humans in vivo indicate that novel metabolic pathways exist in humans. CONCLUSIONS: In summary, the metabolism of gefitinib in humans in vivo is extensive and complex. Based on in vivo evidence, the propoxy-morpholine ring side chain and O-methyl group are the critical metabolic regions of gefitinib in humans. The novel metabolic pathways differ from those of in vitro studies, suggesting that intestinal floral metabolism might be involved.

Clinical features and prognostic factors for surgical treatment of esophageal squamous cell carcinoma in elderly patients.

PURPOSE: This research was designed to analyze the clinical features and prognostic factors for surgical treatment of esophageal squamous cell carcinoma (ESCC) in elderly patients aged 70 years and over. METHODS: The clinical data and follow-up data of 68 ESCC patients aged 70 years and over were collected. The characteristics of surgical treatment, perioperative complications, overall survival (OS), and the factors affecting survival were analyzed. RESULTS: The incidence rate of postoperative complications was 36% and the mortality rate was 0% during and 90 days after surgery. The 5-year OS was 45.0% and the 5-year disease-free survival (DFS) was 38.0%. Univariate analysis showed that gender, Charlson Comorbidity Index (CCI), pathological type, tumor differentiation, depth of invasion, postoperative complications, and lymph node metastasis were the factors associated with OS. Multivariate analysis showed that pathologic type, depth of invasion, and lymph node metastasis were the independent predictors of OS. The ideal long-term survival in elderly patients with ESCC was achieved with radical resection. CONCLUSION: The pathological type and pathological stage were the important independent risk factors of prognosis.

A novel solid-phase site-specific PEGylation enhances the in vitro and in vivo biostabilty of recombinant human keratinocyte growth factor 1.

Keratinocyte growth factor 1 (KGF-1) has proven useful in the treatment of pathologies associated with dermal adnexae, liver, lung, and the gastrointestinal tract diseases. However, poor stability and short plasma half-life of the protein have restricted its therapeutic applications. While it is possible to improve the stability and extend the circulating half-life of recombinant human KGF-1 (rhKGF-1) using solution-phase PEGylation, such preparations have heterogeneous structures and often low specific activities due to multiple and/or uncontrolled PEGylation. In the present study, a novel solid-phase PEGylation strategy was employed to produce homogenous mono-PEGylated rhKGF-1. RhKGF-1 protein was immobilized on a Heparin-Sepharose column and then a site-selective PEGylation reaction was carried out by a reductive alkylation at the N-terminal amino acid of the protein. The mono-PEGylated rhKGF-1, which accounted for over 40% of the total rhKGF-1 used in the PEGylation reaction, was purified to homogeneity by SP Sepharose ion-exchange chromatography. Our biophysical and biochemical studies demonstrated that the solid-phase PEGylation significantly enhanced the in vitro and in vivo biostability without affecting the over all structure of the protein. Furthermore, pharmacokinetic analysis showed that modified rhKGF-1 had considerably longer plasma half-life than its intact counterpart. Our cell-based analysis showed that, similar to rhKGF-1, PEGylated rhKGF-1 induced proliferation in NIH 3T3 cells through the activation of MAPK/Erk pathway. Notably, PEGylated rhKGF-1 exhibited a greater hepatoprotection against CCl(4)-induced injury in rats compared to rhKGF-1.