sPD-L1 and sPD-L2 in plasma of patients with lung cancer and their clinical significance.

INTRODUCTION: Lung cancer is the leading cause of cancer death worldwide. We aim here to determine the soluble programmed death ligand-1 (sPD-L1) and soluble programmed death ligand-2 (sPD-L2) levels in the plasma of patients with lung cancer and evaluate the clinical significance. METHODS: Plasma samples from 95 lung cancer patients and 55 healthy donors were collected, and the sPD-L1 and sPD-L2 levels were measured using the enzyme-linked immunosorbent assay. The correlations of the plasma sPD-L1 and sPD-L2 levels with clinicopathological status and survival of the patients were analyzed. RESULTS: The sPD-L1 and sPD-L2 levels in plasma of lung cancer patients were 713.8 (240.6-3815) pg/ mL and 3233(1122-13955) pg/ mL, respectively, which were significantly higher than those of the health donors 618.6 (189.1-1149) pg/ mL and 2182 (1133-3471) pg/ mL, and the plasma levels of sPD-L1 are correlated with sPD-L2. ROC results showed that both sPD-L1 and sPD-L2 were potential biomarker for lung cancer, and with a higher accuracy level when combined with CEA. Patients with Higher plasma sPD-L1 level (>713.75 pg/ mL) are associated with poor overall survival in advanced lung cancer patients (197 days vs 643 days). CONCLUSIONS: The combination of sPD-L1 and sPD-L2 could be used as adjunctive diagnostic, High level of plasma sPD-L1 rather than sPD-L2 is associated with poor prognosis in lung cancer patients.

Extensive antimicrobial resistance and plasmid-carrying resistance genes in mcr-1-positive E. coli sampled in swine, in Guangxi, South China.

BACKGROUND: The discovery of the superbug mcr-1-positive Escherichia coli (MCRPEC) has drew greet attention. Swine-origin multi-drug resistant MCRPEC has been a potential threat to public health and safety. However, there were few detailed studies have been reported on swine MCRPEC in Guangxi, South China. RESULTS: In this study, thirty-three MCRPEC strains were detected from 142 E. coli strains from 116 samples in Guangxi in 2018. Which could be classified into eight unique STs and a total of six incompatibility plasmid groups (IncFI, IncHI1, IncY, IncN, IncI1 and IncX1). After that, the susceptibility of MCRPEC isolates to 27 antimicrobial agents belonging to 17 antimicrobial categories was tested. There were nineteen E. coli resistant to 3rd and 4th generation cephalosporins and twelve E. coli resistant to carbapenem resistan. Importantly, the MCRPEC showed high resistance highly resistance for imipenem and meropenem, which were forbidden to use in livestock production. Three MCRPEC strains were further proved to be extensively drug-resistant (XDR), and the other isolates were multi-drug-resistant (MDR). Furthermore, we found that the plasmid-carrying resistance genes coexisted with the mcr-1 gene of the MCRPEC isolates. Which were listed as follows: ß-lactamase antimicrobial resistance genes e.g. ESBL genes (blaCTX-M14, blaCTX-M24, blaCTX-M123, blaOXA-1), plasmid-mediated AmpC (pAmpC) gene (blaCMY-2), the carbapenem resistance gene (blaNDM-5), and non-ß-lactamase antimicrobial resistance genes (qnrA, qnrB, qnrS, aac (6')-Ib-cr, tetA, tetB, sul1, sul2, floR, aadA). CONCLUSION: Thirty-three mcr-1-positive E. coli isolates in Guangxi displayed a wide profile of antimicrobial resistance. Plasmid-carrying resistance genes might be the main cause of MCRPEC multidrug resistance. This study highlighted the necessity for long-term surveillance of mcr-1-positive E. coli in pigs.

Identification and complete genome of lytic "Kp34likevirus" phage vB_KpnP_Bp5 and therapeutic potency in the treatment of lethal Klebsiella pneumoniae infections in mice.

Klebsiella pneumoniae (K. pneumoniae) infection exist widely in the farming and medical. The treatment of K. pneumoniae infection is primarily based on antibiotics, which not only leads to a large economic burden but also the development of antibiotic resistance. Bacteriophages therapy present a promising alternative. The object of this study was identifying comprehensively a lytic lethal K. pneumoniae phage vB_KpnP_Bp5, and evaluating the phage as an anti-infective agent in an experimental K. pneumoniae infection murine model. The phage Bp5 had the following characteristics: the optimal number of infections was 0.001, the latent period was 5 min, the outbreak period was 40 min, the burst size was 24 plaque-forming unit (PFU)/cell, the phage could withstand 50 °C temperature and the optimal pH value was 4.0-10.0. According to electron microscopy and whole-genome sequence analysis, the phage should be classified as a member of order Caudovirales, family Podoviridae, subfamily Autographiviridae. Meantime, phylogenetic analysis showed high conservation of gene arrangement and gene content. We demonstrated that administration of phage Bp5 significantly reduced colony formation by K. pneumoniae and alleviated damage to lung tissue. In addition, different therapy time point was closely related to body health and the degree of tissue damage. Once treated promptly, it will greatly reduce mortality and alveolar inflammatory exudation and injury.

RFRP-3, the Mammalian Ortholog of GnIH, Is a Novel Modulator Involved in Food Intake and Glucose Homeostasis.

RF amide-related peptide 3 (RFRP-3) is a reproductive inhibitor and an endogenous orexigenic neuropeptide that may be involved in energy homeostasis. In this study, we evaluated the effect of acute or chronic RFRP-3 treatment (administered via intraperitoneal injection) on the food intake, meal microstructure and weight of rats, as well as the mechanism through which RFRP-3 is involved in glucose metabolism in the pancreas and glucose disposal tissues of rat in vivo. Our results showed that the intraperitoneal administration of RFRP-3 to rats resulted in marked body mass increased, hyperphagia, hyperlipidemia, hyperglycemia, glucose intolerance, hypoinsulinism, hyperglucagon, and insulin resistance, as well as significant increases in the size of pancreatic islets and the inflammatory reaction. Thus, we strongly assert that RFRP-3 as a novel neuroendocrine regulator involved in blood glucose homeostasis.