Background Effective and accurate screening of oncological biomarkers in peripheral blood circulation plays an increasingly vital role in diagnosis and prognosis. High-sensitivity assays can effectively aid clinical decision-making and intervene in cancer in a localized status before they metastasize and become unmanageable. Meanwhile, it is equally pivotal to prevent overdiagnosis of non-life-threatening cancer by eliminating unnecessary treatment and repeated blood draws. Unfortunately, current clinical screening methodologies can hardly simultaneously attain sufficient sensitivity and specificity, especially under resource-restrained circumstances. To circumvent such limitations, particularly for cancer biomarkers from early-onset and recurrence, we aim to develop a universal plasmonic platform for clinical applications, which macroscopically amplifies multiplexed fluorescence signals in a broad spectral window and readily adapts to current assay setups without sophisticated accessories or expertise at low cost. Methods The plasmonic substrate was chemically synthesized in situ at the solid–liquid interface by rationally screening a panel of reducing monosaccharides and tuning the redox reactions at various catalyst densities and precursor concentrations. The redox properties were studied by Benedict’s assay and electrochemistry. We systemically characterized the morphologies and optical properties of the engineered plasmonic Ag structures by scanning electron microscopy (SEM) and spectroscopy. The structure-fluorescence enhancement correlation was explicitly explained by the finite-difference time-domain (FDTD) simulation and a computational model for gap distribution. Next, we established an enhanced fluoroimmunoassay (eFIA) using a model biomarker for prostate cancer (PCa) and validated it in healthy and PCa cohorts. Prognosis was explored in patients subject to surgical and hormonal interventions following recommended PCa guidelines. Results The monosaccharide-mediated redox reaction yielded a broad category of Ag structures, including sparsely dispersed nanoparticles (NPs) of various sizes, semi-continuous nanoislands, and crackless continuous films. Optimal broad-spectral fluorescence enhancement from green to far-red was observed for the inhomogeneous, irregularly-shaped semi-continuous Ag nanoisland substrate (AgNIS), synthesized from a well-balanced redox reaction at a stable rate mediated by mannose. In addition, different local electric field intensity distributions in response to various incident excitations were observed at the nanoscale, elucidating the need for irregular and inhomogeneous structures. AgNIS enabled a maximized 54.7-fold macroscopically amplified fluorescence and long-lasting photostability. Point-of-care availability was fulfilled using a customized smartphone prototype with well-paired optics. The eFIA effectively detected the PCa marker in cell lines, xenograft tumors, and patient sera. The plasmonic platform rendered a diagnostic sensitivity of 86.0% and a specificity of 94.7% and capably staged high-grade PCa that the clinical gold standard test failed to stratify. Patient prognosis of robotic-assisted surgeries and hormone therapies was non-invasively monitored following efficient medical interventions. The assay time was significantly curtailed on the plasmonic platform upon microwave irradiation. Conclusions By investigating the effects of reducing monosaccharides on the seed-mediated chemical synthesis of plasmonic Ag structures, we deduced that potent multiplexed fluorescence enhancement originated from both an adequate reducing power and a steady reduction rate. Furthermore, the inhomogeneous structure with adequate medium gap distances afforded optimal multiwavelength fluorescence enhancement, thus empowering an effective eFIA for PCa. The clinically validated diagnostic and prognostic features, along with the low sample volume, point-of-care feasibility with a smartphone, and microwave-shortened assay time, warrant its potential clinical translation for widespread cancer biomarker analysis. Graphical Abstract
Background: Nonmuscle invasive bladder cancer is a common malignancy of the urinary system. Many patients relapse after transurethral resection surgery. Different anaesthesia techniques may influence a patient’s immune system during the perioperative time. Here, we studied the effects of different anaesthesia techniques on the prognosis of primary nonmuscle invasive bladder cancer after transurethral resection surgery. Methods: From 2008 to 2017, a total of 926 patients suffered primary nonmuscle invasive bladder and accepted transurethral resection of bladder tumour surgery for the first time. They were divided into two groups based on the techniques that were used. The general anaesthesia group contained 662 patients, who received propofol, opioid drugs (fentanyl family), non-depolarizing muscle relaxants, and sevoflurane, and the epidural anaesthesia group contained 264 patients, who had an epidural catheter placed in the L2-L3 or L3-L4 interspace with a combination of lidocaine and ropivacaine or bupivacaine. We studied the influence factors that could affect prognosis and compared the recurrence-free survival time and the progression of the two groups.Results: The differences between the two groups in recurrence rate and progression rate were not statistically significant. Progression-free survival time of epidural anaesthesia group was longer. Multivariate regression analysis showed that anaesthesia techniques were not independent influencing factors for recurrence and progression. Conclusions: In this study, it was not found that anaesthesia techniques could influence the recurrence or progression of patients with primary nonmuscle invasive bladder cancer after transurethral resection of bladder tumour.
Background: Few studies have suggested the correlation between intraoperative dexamethasone and oncological outcomes in non-small cell lung cancer (NSCLC) patients with radical resection. The existing data are inconsistent and inadequate, and more evidence is needed. We therefore undertook a propensity-matched cohort study to investigate the correlation. Methods: 832 patients with stage I to IIIa NSCLC who went through a curative resection between January 2008 and December 2013 were enrolled in our study. Propensity-score matching analysis created a population of 206 patients in the non-DEX group and 103 patients in the DEX group. Cox regression analyses were applied to compare the disease-free survival (DFS) and overall survival (OS) between patients who did not and did receive dexamethasone in the propensity score-matched cohort, as well as in the certain patients with high-risk factors of postoperative nausea and vomiting. Results: After propensity score matching, intraoperative dexamethasone was not significantly associated with DFS (HR: 1.014, 95%CI: 0.786-1.309, P = 0.913) and OS (HR: 1.221, 95%CI: 0.905-1.647, P = 0.191). Multivariable cox regression analysis revealed that intraoperative dexamethasone was not still associated with DFS and OS after curative resection for NSCLC. In the subgroup analysis, intraoperative dexamethasone was significantly associated with improved DFS (HR: 0.20, 95%CI: 0.04-0.92, P = 0.038) in the group of anesthetic time less than 2 hours. In the subgroup of VATS, intraoperative dexamethasone was significantly associated with prolonged OS (HR: 0.53, 95%CI: 0.30-0.92, P = 0.023). Conclusion: There was no correlation between intraoperative administration of dexamethasone and survival in NSCLC patients after curative surgery. While patients given intraoperative dexamethasone had better disease-free survival compared with patients not given intraoperative dexamethasone in the subgroup of anesthetic time less than 2 hours. Intraoperative administration of dexamethasone may improve overall survival in the subgroup of VATS. Our results indicate that intraoperative administration of dexamethasone is probably favorable in the aforementioned populations.
Background: Few studies have suggested the correlation between intraoperative dexamethasone and oncological outcomes in non-small cell lung cancer (NSCLC) patients with radical resection. The existing data are inconsistent and inadequate, and more evidence is needed. We therefore undertook a propensity-matched cohort study to investigate the correlation.Methods: 832 patients with stage I to IIIa NSCLC who went through lung tumor resection between January 2008 and December 2013 were enrolled in our study. Propensity-score matching analysis created a population of 260 patients in the non-DEX group and 130 patients in the DEX group. Cox regression analyses were applied to compare the disease-free survival (DFS) and overall survival (OS) between patients who did not and did receive dexamethasone in the propensity score-matched cohort, as well as in the certain patients with high-risk factors of postoperative nausea and vomiting (PONV).Results: After propensity score matching, intraoperative dexamethasone was not significantly associated with DFS (HR: 0.944, 95%CI: 0.720-1.237, P = 0.655) and OS (HR: 1.210, 95%CI: 0.927-1.581, P = 0.486). Multivariable cox regression analysis revealed that intraoperative dexamethasone was not independent prognostic factor for DFS and OS in NSCLC patients undergoing surgical resection. In the subgroup analysis, including female subgroup, nonsmoking subgroup, long anesthetic time subgroup, VATS subgroup and inhaled anesthetics subgroup, intraoperative dexamethasone was not significantly associated with DFS and OS.Conclusion: There was no correlation between intraoperative administration of dexamethasone and survival in NSCLC patients after curative surgery. In the high-risk subgroups of PONV, that is, female, nonsmoking, long anesthetic time, VATS and inhaled anesthetics, patients given intraoperative dexamethasone had no better or poorer prognosis compared with patients not given intraoperative dexamethasone.
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