Inflammation is a component of tumor progression mechanisms. Neutrophils are a common inflammatory infiltrate in many tumors, but their regulation and functions in neoplasia are not understood. Here, we showed, in detailed studies of c-Met molecule in 225 untreated patients with hepatocellular carcinoma (HCC), that high infiltration of neutrophils in HCC tissues determined malignant cell c-Met-associated clinical outcome of patients. High infiltration of neutrophils in HCCs determined malignant cell c-Metassociated clinical outcome of patients. Neutrophils were enriched predominantly in invading tumor edge of HCCs; the accumulated neutrophils were the major source of c-Met ligand HGF in HCCs. Exposure to HCC environments resulted in neutrophil activation and the following HGF production. Inhibiting the activities of Erk1/2, p38, and NF-kB, but not the phosphorylation of AKT or JNK, successfully attenuated the neutrophil HGF production induced by HCC environments. Further investigation revealed that GM-CSF was an important determinant in malignant cell-elicited neutrophil HGF production in vitro and in vivo. Moreover, we demonstrated that tumor neutrophils, via HGF/c-Met interaction, actively enhanced the metastasis of malignant cells in vitro and in vivo. These data provide direct evidence supporting the critical role of neutrophils in human tumor progression and reveal a fine-tuned collaborative action between cancer cells and immune cells in tumor milieu, which reroutes the immune activation into a tumorpromoting direction.

Objective To understand the bacterial profile and antibiotic resistance patterns in diabetic foot infection (DFI) in different Wagner's grades, IDSA/IWGDF grades, and different ulcer types in Guangzhou, in order to provide more detailed suggestion to the clinician about the empirical antibiotic choice. Methods 207 bacteria were collected from 117 DFIs in Sun Yat-sen Memorial Hospital from Jan.1, 2010, to Dec.31, 2015. The clinical data and microbial information were analyzed. Results The proportion of Gram-negative bacteria (GNB) was higher than Gram-positive bacteria (GPB) (54.1% versus 45.9%), in which Enterobacteriaceae (73.2%) and Staphylococcus (65.2%) were predominant, respectively. With an increasing of Wagner's grades and IDSA/IWGDF grades, the proportion of GNB bacterial infection, especially Pseudomonas, was increased. Neuro-ischemic ulcer (N-IFU) was more susceptible to GNB infection. Furthermore, with the aggravation of the wound and infection, the antibiotic resistance rates were obviously increased. GPB isolated in ischemic foot ulcer (IFU) showed more resistance than the N-IFU, while GNB isolates were on the opposite. Conclusions Different bacterial profiles and antibiotic sensitivity were found in different DFU grades and types. Clinician should try to stay updated in antibiotic resistance pattern of common pathogens in their area. This paper provided them the detailed information in this region.

Coronavirus disease 2019 (COVID‐19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). In China, Yinqiao powder is widely used to prevent and treat COVID‐19 patients with Weifen syndrome. In this study, the screening and verification of active ingredients, target selection and DisGeNET scoring, drug–ingredient–gene network construction, protein–protein interaction network construction, molecular docking and surface plasmon resonance (SPR) analysis, gene ontology (GO) functional analysis, gene tissue analysis, and kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were used to explore the active ingredients, targets, and potential mechanisms of Yinqiao powder in the treatment of COVID‐19. We also predicted the therapeutic effect of Yinqiao powder using TCM anti‐COVID‐19 (TCMATCOV). Yinqiao powder has a certain therapeutic effect on COVID‐19, with an intervention score of 20.16. Hesperetin, eriodictyol, luteolin, quercetin, and naringenin were the potentially effective active ingredients against COVID‐19. The hub‐proteins were interleukin‐6 (IL‐6), mitogen‐activated protein kinase 3 (MAPK3), tumor necrosis factor (TNF), and tumor protein P53 (TP53). The potential mechanisms of Yinqiao powder in the treatment of COVID‐19 are the TNF signaling pathway, T‐cell receptor signaling pathway, Toll‐like receptor signaling pathway, and MAPK signaling pathway. This study provides a new perspective for discovering potential drugs and mechanisms of COVID‐19.

Background: Total flavonoids of Rhizoma Drynariae (TFRD), extracted from the kidney-tonifying traditional Chinese medicine Rhizoma Rrynariae, has been proved to be effective in treating osteoporosis, bone fractures and defects. However, pharmacological effects of TFRD on type H vessels, angiogenic-osteogenic coupling in distraction osteogenesis (DO) and the mechanism remain unclear. This study aims at investigating whether type H vessels exist in the DO model, effects of TFRD on angiogenic-osteogenic coupling and further elucidating the underlying mechanism.Methods: Rats models of DO and bone fracture (FR) were established, and then were separately divided into TFRD and control subgroups. Imageological and histological analyses were performed to assess bone and vessel formation. Immunofluorescent staining of CD31 and endomucin (Emcn) was conducted to determine type H vessel formation. Matrigel tube formation, ALP and Alizarin Red S staining assays were performed to test the effects of TFRD on angiogenesis or osteogenesis of endothelial precursor cells (EPCs) or bone marrow-derived mesenchymal stem cells (BMSCs). Additionally, expression levels of HIF-1α, VEGF, PDGF-BB, RUNX2 and OSX were determined by ELISA, qPCR or western blot, respectively.Results: The in vivo results indicated more formed type H vessels in DO groups than in FR groups and TFRD obviously increased the abundance of type H vessels. Moreover, groups with higher abundance of type H vessels showed better angiogenesis and osteogenesis outcomes. Further in vitro experiments showed that TFRD significantly promoted while blocking PDGF-BB remarkably suppressed the angiogenic activity of EPCs under stress conditions. The levels of p-AKT and p-ERK1/2, downstream mediators of the PDGF-BB pathway, were up-regulated by TFRD but blocked by function blocking anti-PDGF-BB antibody. In contrast, the activated AKT and ERK1/2 and corresponding tube formation were not affected by the HIF-1α inhibitor. Besides, blocking PDGF-BB inhibited the osteogenic differentiation of the stretched BMSCs, but TFRD enhanced the osteogenic activity of BMSCs and ameliorated the inhibition, with more calcium nodes, higher ALP activity and mRNA and protein levels of RUNX2 and OSX.Conclusion: Type H vessels exist in the DO model and TFRD enhances angiogenic-osteogenic coupling during DO by promoting type H vessel formation via PDGF-BB/PDGFR-β instead of HIF-1α/VEGF axis.