RNA-seq Analysis of Spinal Cord Tissues after Brachial Plexus Root Avulsion in Mice

Background Brachial plexus root avulsion (BPRA) can cause motor neuron death, nerve degeneration andupper limb motor dysfunction. The molecular mechanisms of motor neuron death and nerve degeneration arelargely unknown and there are no effective therapies to increase the functional recovery after BRPA.Aim: To detect the early pathway changes in spinal cord tissues after brachial plexus root avulsion.Methods A mouse brachial plexus avulsion and re-implantation model was constructed, and the C5-C7segments of the spinal cords were dissected three days after the surgery. We used RNA-seq to identify theexpression changes of genes and gene networks in spinal cord tissues.Results A total of 2253 differentially expressed genes were found significantly changed with 1852 upregulatedand 401 downregulated at 3 days after BPRA. Gene ontology (GO) enrichment analysis showed thatdifferentially expressed genes were most enriched in immune system process, regulation of immune systemprocess, defense response, plasma membrane part, extracellular region part, cell surface, protein binding,receptor binding, glycosaminoglycan binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathwayanalysis showed that the most enriched pathways included osteoclast differentiation, NF-kappa B, cytokinecytokine receptor interaction, TNF, hematopoietic cell lineage, complement and coagulation cascades, PI3KAkt, ECM-receptor interaction, NOD-like receptor, Toll-like receptor signaling pathway.Conclusions This study systematically identified the critical genes and signaling pathways in BPRA pathology.These results expand our understanding of the complex molecular mechanisms involved in BPRA and provide afoundation for future research of spinal cord tissue injury and repair.

Hyperprogressive disease in cancer patients with immune checkpoint inhibitor therapy and its coping strategies / 中国肿瘤生物治疗杂志

@#Successful targeting and inhibition of the programmed cell death-1/ programmed cell death-ligand 1 immune checkpoint pathways by monoclonal antibody stimulates an immune response against tumors, has led to a rapidly expanding repertoire of immune checkpoint inhibitors (ICIs) for the treatment of various cancers. Immune checkpoint therapy has dramatically changed the therapeutic landscape of certain types of cancers. However, hyperprogressive disease (HPD) is emerging as a new pattern of progression in cancer patients treated with ICIs, characterized as an absolute increase in the tumor growth rate exceeding 50% per month. This article discusses the concept of HPD, hypotheses as to the underlying biology, and what needs to be done to better understand and identify strategies to prevent or overcome HPD related to checkpoint blockade therapy.