Enhanced Label-Free Nanoplasmonic Cytokine Detection in SARS-CoV-2 Induced Inflammation Using Rationally Designed Peptide Aptamer.

Rapid and precise serum cytokine quantification provides immense clinical significance in monitoring the immune status of patients in rapidly evolving infectious/inflammatory disorders, examplified by the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. However, real-time information on predictive cytokine biomarkers to guide targetable immune pathways in pathogenic inflammation is critically lacking, because of the insufficient detection range and detection limit in current label-free cytokine immunoassays. In this work, we report a highly sensitive localized surface plasmon resonance imaging (LSPRi) immunoassay for label-free Interleukin 6 (IL-6) detection utilizing rationally designed peptide aptamers as the capture interface. Benefiting from its characteristically smaller dimension and direct functionalization on the sensing surface via Au-S bonding, the peptide-aptamer-based LSPRi immunoassay achieved enhanced label-free serum IL-6 detection with a record-breaking limit of detection down to 4.6 pg/mL, and a wide dynamic range of ∼6 orders of magnitude (values from 4.6 to 1 × 106 pg/mL were observed). The immunoassay was validated in vitro for label-free analysis of SARS-CoV-2 induced inflammation, and further applied in rapid quantification of serum IL-6 profiles in COVID-19 patients. Our peptide aptamer LSPRi immunoassay demonstrates great potency in label-free cytokine detection with unprecedented sensing capability to provide accurate and timely interpretation of the inflammatory status and disease progression, and determination of prognosis.

Predicting miRNA-disease association through combining miRNA function and network topological similarities based on MINE.

Predicting associations between microRNAs (miRNAs) and diseases from the viewpoint of function modules has become increasingly popular. However, existing methods obtained the relations between diseases and miRNAs only through the construction of similarity networks and neglected the complex network characteristic. In this paper, a new method named combining miRNA function similarities and network topology similarities based on module identification in networks (ComSim-MINE) was developed. Combined similarity is calculated from the harmonic mean between miRNA function similarities and network topology similarities. Experimental results showed that ComSim-MINE can compete with several state-of-the-art weighted function module algorithms, such as ClusterONE, MCODE, NEMO, and SPICi, and achieved the satisfactory results in terms of the composite score of F-measure, sensitivity, and accuracy based on the generated miRNA function interaction network. From the analysis of case studies, some new findings obtained from our proposed method provide clinicians new clues for epidemic diseases, such as COVID-19.

Efficacy, Safety, and Impact on Patient Survival of PDL1/PD-1 Inhibitors versus FOLFIRINOX Regimens for Advanced Pancreatic Cancer.

Background: Over the last few years, the role of PDL1/PD-1 in pancreatic cancer development has received increasing attention, and this article is aimed at opening up new ideas for the medicine-based treatment of pancreatic cancer. Aims: To investigate the efficacy and safety of PDL1/PD-1 inhibitors versus FOLFIRINOX regimen in the treatment of advanced pancreatic cancer and its impact on patient survival and to provide a reference basis for clinical treatment of pancreatic cancer. Materials and Methods: The 116 pancreatic cancer patients treated in our hospital from September 2019 to September 2021 were selected and divided into 58 cases each in the (instance of watching, noticing, or making a statement) group and the comparison group according to the method based on random number table. The comparison group was treated with FOLFIRINOX, and the group was treated with PDL1/PD-1 stopper. The effectiveness, safety, and hit/effect on survival of the patients in the two groups were compared. Results: The median chemotherapy cycle for all patients was 4 (1-6), and the combined objective remission rate (0RR) was 36% and the disease control rate (DCR) was 80% after no chemotherapy in 116 patients, with 37.5% 0RR and 81.3% DCR in the observation group and 33.3% 0RR and 77.8% DCR in the comparison group. The greatest number of all patients reached SD, 44%; in the observation group, 43.8%; and in the comparison group, 44.5%. The rate of adverse reactions such as hematological toxicity, neutropenia, anemia, thrombocytopenia, nonhematological toxicity, vomiting, fatigue, infection, diarrhea, intestinal obstruction, and peripheral neuropathy was lower in 10.3% of patients in the observation group than in 25.8% of patients in the comparison group, which was significantly different by χ 2 test (P < 0.05). The median progression-free survival curve of the two groups was 19 months in the comparison group and 22 months in the observation group. The progression-free survival in the observation group was significantly higher than that in the comparison group, and there was a statistically significant difference between the two groups (P < 0.05). Conclusion: PDL1/PD-1 inhibitors in combination with FOLFIRINOX regimens have shown longer survival than treatment with FOLFIRINOX regimens for pancreatic cancer patients, with reliable clinical efficacy, tolerable adverse effects, and a high safety profile for patients.