The viral distribution and pathological characteristics of BALB/c mice infected with highly pathogenic Influenza H7N9 virus.

BACKGROUND: The highly pathogenic Influenza H7N9 virus is believed to cause multiple organ infections. However, there have been few systematic animal experiments demonstrating the virus distribution after H7N9 virus infection. The present study was carried out to investigate the viral distribution and pathological changes in the main organs of mice after experimental infection with highly pathogenic H7N9 virus. METHODS: Infection of mice with A/Guangdong/GZ8H002/2017(H7N9) virus was achieved via nasal inoculation. Mice were killed at 2, 3, and 7 days post infection. The other mice were used to observe their illness status and weight changes. Reverse transcription polymerase chain reaction and viral isolation were used to analyse the characteristics of viral invasion. The pathological changes of the main organs were observed using haematoxylin and eosin staining and immunohistochemistry. RESULTS: The weight of H7N9 virus-infected mice increased slightly in the first two days. However, the weight of the mice decreased sharply in the following days, by up to 20%. All the mice had died by the 8th day post infection and showed multiple organ injury. The emergence of viremia in mice was synchronous with lung infection. On the third day post infection, except in the brain, the virus could be isolated from all organs (lung, heart, kidney, liver, and spleen). On the seventh day post infection, the virus could be detected in all six organs. Brain infection was detected in all mice, and the viral titre in the heart, kidney, and spleen infection was high. CONCLUSION: Acute diffuse lung injury was the initial pathogenesis in highly pathogenic H7N9 virus infection. In addition to lung infection and viremia, the highly pathogenic H7N9 virus could cause multiple organ infection and injury.

Disseminated Nocardia infection with a lesion occupying the intracranial space complicated with coma: a case report.

BACKGROUND: Disseminated Nocardia infection is a disease that is easily overlooked in patients with lesions occupying the intracranial space complicated with coma. Early diagnosis and treatment are crucial. CASE PRESENTATION: A 65-year-old man was admitted to the First Affiliated Hospital of Zhejiang University in October 2018 with weakness in the right limbs for 3 days and altered consciousness for 1 day. Five months earlier, he had been diagnosed with membranous kidney disease and had received cyclophosphamide and prednisone. At admission, the white blood cell count was 1.37 × 1010/L (with 86.4% neutrophils), and C-reactive protein was 115.60 mg/L. Imaging examinations revealed a lesion occupying the intracranial space, lung infection, and multiple abscesses in the rhomboid muscle. The abscesses were drained. Pus culture confirmed Nocardia cyriacigeorgica infection. With antibiotics and vacuum-sealed drainage of the back wound, the patient improved and was discharged from the hospital. CONCLUSIONS: This case report shows that infection should be considered during the differential diagnosis of lesions in the intracranial space, especially in patients receiving immunosuppressive treatment. In patients with disseminated N. cyriacigeorgica infection, combination antibiotic therapy and surgical drainage of localised abscesses can be effective.

Novel pathogenic characteristics of highly pathogenic avian influenza virus H7N9: viraemia and extrapulmonary infection.

The H7N9 virus mutated in 2017, resulting in new cases of highly pathogenic avian influenza (HPAI) H7N9 virus infection. H7N9 was found in a viraemic patient in Guangdong province, China. The present study aimed to clarify the pathogenic characteristics of HPAI H7N9. Virus was isolated from the plasma and sputum of the patient with HPAI H7N9. Liquid phase chip technology was used to detect the plasma cytokines from the infected patient and healthy controls. Mice were infected with strains A/Guangdong/GZ8H002/2017(H7N9) and A/Zhejiang/DTID-ZJU01/2013(H7N9) to observe the virus's pathogenic characteristics. Serum and brain tissue were collected at 2, 4, and 6 days after infection. The viruses in serum and brain tissue were detected and isolated. The two strains were infected into A549 cells, exosomes were extracted, and virus genes in the exosomes were assessed. Live virus was isolated from the patient's plasma. An acute cytokine storm was detected during the whole course of the disease. In animal experiments, A/Guangdong/GZ8H002/2017(H7N9) was more pathogenic than A/Zhejiang /DTID-ZJU01/2013(H7N9) and resulted in the death of mice. Live virus was isolated from infected mouse serum. Virus infection was also detected in the brain of mice. Under viral stress, A549 cells secreted exosomes containing the entire viral genome. The viraemic patient was confirmed to have an HPAI H7N9 infection. A/Guangdong/GZ8H002/2017(H7N9) showed significantly enhanced toxicity. Patient deaths might result from cytokine storms and brain infections. Extrapulmonary tissue infection might occur via the exosome pathway. The determined pathogenic characteristics of HPAI H7N9 will contribute to its future treatment.

Effect of Calcium Alginate Microsphere Loaded With Vascular Endothelial Growth Factor on Adipose Tissue Transplantation.

Revascularization in the early period after transplantation is the key to improving adipocyte survival. Vascular endothelial growth factor (VEGF) is known as the master regulator of angiogenesis. However, consensus is lacking regarding safe and efficient methods for applying VEGF in free fat transplantation in the clinical setting. We constructed calcium alginate (CA) microspheres loaded with VEGF to increase the survival of implanted adipocytes. BALB/c nude mice were used as adipose tissue transplantation receptors. Adipocytes were mixed with CA microspheres loaded with VEGF and implanted subcutaneously into the dorsum of mice. Grafts were harvested at week 3, 6, and 12 after transplantation. We found that the mass and microvascular density of grafts in the VEGF+CA group (CA microspheres loaded with VEGF) were statistically higher than that of other groups in a time-dependent manner. We demonstrated that CA microspheres loaded with VEGF can significantly promote the fat graft neovascularization, thus improving adipocyte survival.

Effect of chitosan nanospheres loaded with VEGF on adipose tissue transplantation: a preliminary report.

Neovascularization plays an important role in adipose tissue transplantation, because survival of implanted cells strongly relies on sufficient oxygen and nutrient supply. Vascular endothelial growth factor (VEGF) is known as the master regulator of angiogenesis. It is capable of starting the complex cascade of events leading to endothelial cell activation, assembly of new vascular structures, mural cell recruitment, and vessel stabilization. However, consensus is lacking regarding safe and efficient methods for applying VEGF in free fat transplantation in the clinical setting. We investigated whether chitosan nanospheres, a biocompatible high-molecular-weight material, safely improve the efficiency of VEGF application in free fat transplantation. Immunologically compromised nude mice were used as adipose tissue transplantation receptors. Nanospheres loaded with VEGF were mixed with adipocytes and injected subcutaneously to the dorsa of mice. Grafts were harvested at weeks 3, 6, and 12. We found that treated-graft weight and vascularization were significantly higher than controls in a time-dependent manner. We demonstrated that chitosan nanospheres loaded with VEGF significantly promote the fat graft neovascularization and improve adipocyte survival.