Sepsis is a global medical issue owing to its unacceptably high mortality rate. Therefore, an effective approach to predicting patient outcomes is critically needed. We aimed to search for a novel 28-day sepsis mortality prediction model based on serial interleukin-6 (IL-6), lactate (LAC), and procalcitonin (PCT) measurements. We enrolled 367 septic patients based on Sepsis-3 (Third International Consensus Definitions for Sepsis and Septic Shock). Serum IL-6, LAC, and PCT levels were measured serially. Results collected within 24 and 48–72 h of admission were marked as D1 and D3 (e.g., IL-6D1/D3), respectively; the IL-6, LAC, and PCT clearance (IL-6c, LACc, PCTc) at D3 were calculated. Data were split into training and validation cohorts (7:3). Logistic regression analyses were used to select variables to develop models and choose the best one according to the Akaike information criterion (AIC). Receiver operating characteristic curves (ROC), calibration plots, and decision curve analysis (DCA) were used to test model performance. A nomogram was used to validate the model. There were 314 (85.56%) survivors and 53 (14.44%) non-survivors. Logistic regression analyses showed that IL-6D1, IL-6D3, PCTD1, PCTD3, and LACcD3 could be used to develop the best prediction model. The areas under the curves (AUC) of the training (0.849, 95% CI: 0.787–0.911) and validation cohorts (0.828, 95% CI: 0.727–0.929), calibration plot, and the DCA showed that the model performed well. Thus, the predictive value of the risk nomogram was verified. Combining IL-6D1, IL-6D3, PCTD1, PCTD3, and LACcD3 may create an accurate prediction model for 28-day sepsis mortality. Multiple-center research with a larger quantity of data is necessary to determine its clinical utility.

Prostate specific membrane antigen (PSMA) is overexpressed on prostate tumor cells and the neovascular endothelia various solid tumors. A bivalent immunotoxin generated by fusing a fold‐back single‐chain diabody derived from the Fv fragments of an anti‐PSMA monoclonal antibody with a truncated diphtheria toxin (DT) containing the activity and translocation domains [A‐dmDT390‐scfbDb(PSMA)] might be suitable for targeted therapy of tumors that overexpress PSMA. In this study, a PSMA‐positive and a PSMA‐negative prostate cancer cell lines were treated with immunotoxin A‐dmDT390‐scfbDb(PSMA) in order to study the tumor targeting specificity and therapeutic potential of the immunotoxin. The cellular uptake and selective toxicity of the immunotoxin were evident in monolayer cultures of PSMA‐positive LNCaP prostate cancer cells but not in cultures of PSMA‐negative PC‐3 prostate cancer cells. Cellular accumulation of A‐dmDT390‐scfbDb(PSMA) increased with increasing incubation times and concentrations in LNCaP cells. The proportion of apoptotic LNCaP cells increased upon incubation with increasing doses of the fold‐back immunotoxin. Optical imaging and MRI with the Alexa Fluor 680‐labeled A‐dmDT390‐scfbDb(PSMA) confirmed the specific targeting and therapeutic efficacy of this immunotoxin towards PSMA‐positive LNCaP solid tumor xenografts in athymic nude mice.

Although various strategies have been proposed for enrichment of circulating tumor cells (CTCs), the clinical outcomes of CTC detection are far from satisfactory. The prevailing methodologies for CTC detection are generally oriented toward naturally occurring targets; however, misdetection and interference are prevalent due to the diverse phenotypes and subpopulations of CTCs, which are highly heterogeneous. Here, a CTC isolation system based on the “label-capture-release” process is demonstrated for the precise and highly efficient enrichment of CTCs from clinical blood samples. On the basis of the abnormal glycometabolism of tumor cells, the surface of CTCs can be decorated with artificial azido groups. By utilizing bio-orthogonal plates designed with dibenzocyclooctane (DBCO) and disulfide groups, with the aid of anti-fouling effects, CTCs labeled with azido groups can be captured through a copper-free click reaction and subsequently released via disulfide reduction. The technique has been shown to label tumor cells with the epithelial cell adhesion molecule (EpCAM)+ and EpCAM− phenotypes in both adherent and suspended states. Moreover, it effectively isolates all epithelial, interstitial, and hybrid phenotypes of CTCs from clinical blood samples collected from dozens of patients across more than 10 cancer types. Compared to the clinically approved CTC detection system, our strategy demonstrates superior performance from the perspective of broad-spectrum and accurate recognition of heterogeneous CTCs. More importantly, most of the captured CTCs can be released with the retention of living activity, making this technique well suited for downstream applications such as drug susceptibility tests involving viable CTCs.

Background: Commonly used miRNA detection methods cannot be applied for high-throughput analyses. However, this study was aimed to performed a liquid bead array detection system (LBAS) to detect tissue 6 miRNAs in non-small cell lung cancer (NSCLC). Methods: In this study, evaluation of LBAS was performed to observe the precision, specificity, limitation and stability. Then, a total of 52 primary NSCLC patients who received resection operation without preoperative radiotherapy and chemotherapy between June 2013 and March 2014 were selected, and then the total RNA of the tissues were extracted. We prepared six NSCLC-related miRNAs for LBAS. After optimization and evaluation, LBAS was verified by detecting the relative expression levels of 6 microRNAs in the pathological tissues and corresponding normal tissues of 52 NSCLC patients. Results: The results of evaluation of LBAS showed that the Mean Fluorescence Intensity (MFI) of the reaction only added with chimeric probes and beads showed no significant change after 180 days (P > 0.05). And the intra-assay Coefficient of Variation (CV) was between 1.57 and 3.5%, while the inter-assay CV was between 4.24 and 11.27%, indicating this system was ideal for diagnostic reagents. In addition, only the beads corresponding to the additional miRNAs showed high MFIs from 8426 to 18,769, whereas the fluorescence values of the other beads were under background levels (MFIs = 20 to 55) in each reaction, indicating no cross reactivity among the miRNAs. The limit of detection of miR-21, miR-210, miR-125b, miR-155, miR-375, and miR-31 were 5.27, 1.39, 1.85, 2.01, 1.34, and 2.73 amol/μL, respectively, showing that the lowest detection limit of miRNA by this system was under pM level. Then, the relative expression levels of miR-21, miR-210, miR-125b, miR-155, miR-375, and miR-31 by using this system were significantly correlated with NSCLC (P < 0.05). And the results of AUC method indicated that specific of the LBAS system was 94.2%. Conclusions: Our findings suggest that LBAS was simple, high-throughput, and freely combined with absolute quantification. Thus, this system could be applied for tumor miRNAs detection.