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Background：Pulmonary fibrosis (PF) is a growing clinical problem with limited therapeutic options. Human umbilical cord mesenchymal stromal cell (hucMSC) therapy is being investigated in clinical trials for the treatment of PF patients. However, little is known about the underlying molecular and cellular mechanisms of hucMSC therapy on PF. In this study, the molecular and cellular behavior of hucMSC was investigated in a bleomycin induced mouse PF model. Methods: The effect of hucMSC on mouse lung regeneration was determined by detecting Ki67 expression and Edu incorporation in alveolar type 2 (AT2) and lung fibroblast cells. The hucMSC was transfected to express the membrane localized GFP before transplant into the mouse lung. The cellular behavior of hucMSC in mouse lung was tracked by GFP staining. Single cell RNA sequencing was performed to investigate the molecular mechanism of hucMSC on PF. Results: hucMSCs could alleviate collagen accumulation in lung and decrease the mortality of mouse induced by bleomycin. hucMSCs transplantation promoted AT2 cell proliferation and inhibited lung fibroblast cell proliferation. Mouse lung macrophage phenotype was changed after interacting with hucMSCs. By using single-cell RNA sequencing, a subcluster of interferon-sensitive macrophages were identified after hucMSC infusion. These macrophages elevate the secretion of CXCL9 and CXCL10 following hucMSC infusion and recruit more Treg cells to the injured lung. Conclusions: Our study establishes a link between hucMSCs, macrophage proliferation, and PF with potential applications in PF therapeutics. It provides new insights into how hucMSCs interact with macrophage during the repair process of bleomycin-induced PF and play its immunoregulation function.

As RNA interference (RNAi) received solicitous attention by many for its promising performance in gene therapy recently, and how to obtain a choice small interfering RNA (siRNA) vector has become a moot point at this moment. Exosomes (Exo) show advantages of long survival time in vivo, high transmission efficiency and easy penetration across the blood-brain/spinal cord barrier, renowned as excellent carriers of bioactive substances. Previous studies have confirmed the detrimental effect of connective tissue growth factor (CTGF) on axonal regeneration after spinal cord injury (SCI) via stimulating the unrestricted growth of glial scars. In this study, we applied mesenchymal stem cells (MSCs)-derived Exo as the delivery of synthesized siRNA, which were extracted from rat bone marrow. We constructed exosome-siRNA (Exo-siRNA) that could specifically silence Ctgf gene in the injury sites by electroporation.During the administration, we injected Exo-siRNAs into the tail vein of SCI rats, and their distribution and accumulation in the spinal cord were visualized by in vivo fluorescence imaging. Relevant in vivo and in vitro experiments in this study showed that Exo-siRNA not only effectively inhibited the expressions of Ctgf gene and glial scar formation related proteins, such as GFAP, vimentin fibronectin and laminin, in the injured spinal cord segments, but quenched inflammation, and thwarted neuronal apoptosis and reactive astrocytes and glial scar formation. Besides, it significantly up-regulated several neurotrophic factors and anti-inflammatory factors (e.g., TGF-β1), acting as a facilitator of axon regeneration of nerve-injured motor neurons. Thus, the motor function of SCI rats were remarkably promoted.In conclusion, this study has combined the thoroughness of gene therapy and the excellent drug-loading characteristics of Exo for the precise treatment of SCI, which will shed new light on the drug-loading field of Exo.

Background Chondrosarcoma(ChSa) is a rare malignant tumor. But it’s necessary to discuss the clinical characteristics and treatments for ChSa of paranasal sinus and the skull base.We aimed to Observe the effect of Endoscopic surgical treatment with nasal cavity approach for chondrosarcoma of paranasal sinus and the skull base Methods The clinical characteristics of chondrosarcoma of paranasal sinus and skull base in 10 patients (6 males and 4 females) from 2001 to 2017 were analyzed. They all underwent by endoscopic surgery. The patients’ age ranged from 18 to 47 years, with a median of 35 years. Clinical symptoms: stuffy, nose bleeding, runny, headache, diplopia, eye outreach limited, blurred vision and even blindness. Surgery methods：under nasal endoscopy, after the attachment sites of the tumors to normal tissues were confirmed, the tumors were peeled off along the clear boundary between the tumors and normal tissues, and the potential residual tumor tissues on bones were cleared by a drill. If internal carotid artery (ICA) were involved, flap would be used to protect it. Objectives Results All patients were treated with endoscopic surgery，followed up postoperatively for 24 to 108 months, with a median of 36 months. 8 of 10 patients were no recurrence,2 were alive with tumor. Conclusion Chondrosarcoma of paranasal sinus and skull base can be treated by nasal endoscopic surgery with good clinical results.