RESUMO
Objective: To study the value of three-dimensional(3D) visualization in the diagnosis and surgical treatment for pancreatic tumor. Methods: From June to September 2016, 26 patients with pancreatic tumors in Jinling Hospital, Medical School of Nanjing University were involved. The study included 26 patients(8 females and 18 males) with mean age of (57±12)years (ranging from 23 to 77 years). And there were 20 malignant tumors and 6 benign tumors. All of them were examined with abdominal thin slice CT scanning and the CT images were imported into 3D visualization system for 3D visualization. The main elements examined by 3D visualization included tumor shape, size, and location; distribution and morphology of the peripancreatic lymph node; the relationships among neoplasms, organs and blood vessels. Results: Among the 26 patients, there were 21 cases with pancreatic cancer, of which 15 cases successfully underwent standard pancreatectomy. All patients were operated underwent accurate assessment. The 3D model demonstrated the origination and bifurcations of blood vessels, and the relationships among neoplasms, organs and blood vessels efficiently. The 3D technique could facilitate to evaluate response of neiadjuvant chemotherapy in the pancreatic cancer patients (n=5).3D reconstruction could detect the lymph-node metastases accurately (n=12) in patients with pancreatic cancer. 3D reconstruction were applied to evaluate the the size and range of tumor on 5 cases. Conclusions: 3D reconstruction allows stereoscopic identification of the spatial relationships between physiologic and pathologic structures.The 3D technique could facilitate to evaluate distribution and morphology of the peripancreatic lymph node, and to evaluate the relationships among neoplasms, organs and blood vessels.
Assuntos
Imageamento Tridimensional , Neoplasias Pancreáticas , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Projetos Piloto , Tomografia Computadorizada por Raios XRESUMO
Sustained endoplasmic reticulum (ER) stress has been linked to cell death and the pathogenesis of many liver diseases, including toxic liver, cholestasis, and infectious liver disease. The cellular pathways that attenuate hepatic ER stress have been the focus of many recent studies, but the role of microRNAs (miRNA) in this process remains unknown. Here, we report that one of the most abundant miRNAs in hepatocytes, miR-199a-5p, was elevated in both bile acid- and thapsigargin (TG)-stimulated cultured hepatocytes, as well as in the liver of bile duct-ligated mice. We identify the misfolded protein chaperone GRP78, as well as the unfolded protein response transducers endoplasmic reticulum to nucleus signaling 1 and activating transcription factor 6 as direct targets of miR-199a-5p, and show that endogenous miR-199a-5p represses the 3' untranslated regions (UTRs) of their mRNAs. Through gain-of-function and loss of function approaches, we demonstrate that the elevated miR-199-5p disrupts sustained ER stress and prevents hepatocytes from undergoing bile acid- or TG-induced cell death. Furthermore, we reveal that the transcription factor AP-1 is a strong positive regulator of miR-199a-5p. In brief, our study demonstrates that AP-1/miR-199a-5p and ER stress mediators form a feedback loop, which shields hepatocytes from sustained ER stress and protects the liver from injury. On the basis of these findings, we also suggest that the miRNA miR-199a-5p is a potential target for clinical approaches aiming to protect hepatocytes in liver disease.
Assuntos
Ácidos e Sais Biliares/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hepatócitos/metabolismo , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Fator 6 Ativador da Transcrição/antagonistas & inibidores , Fator 6 Ativador da Transcrição/genética , Fator 6 Ativador da Transcrição/metabolismo , Animais , Apoptose , Células Cultivadas , RNA Helicases DEAD-box/antagonistas & inibidores , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Chaperona BiP do Retículo Endoplasmático , Endorribonucleases/antagonistas & inibidores , Endorribonucleases/genética , Endorribonucleases/metabolismo , Feminino , Células HEK293 , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Hepatócitos/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/metabolismo , Ribonuclease III/antagonistas & inibidores , Ribonuclease III/genética , Ribonuclease III/metabolismo , Tapsigargina/farmacologia , Fator de Transcrição AP-1/metabolismoRESUMO
The Chinese equine infectious anemia virus (EIAV) donkey-leukocyte attenuated vaccine (DLV) provides a unique natural model system to study the attenuation mechanism and immunological control of lentivirus replication. Critical consensus mutations were identified between virulent Chinese EIAV strains and vaccine strains. Based on a full-length infectious clone of EIAV vaccine strain pLGFD3, two molecular clones, mFD5-4-7 and mFD7-2-11, were successfully constructed, in which 4 and 6 critical consensus mutations in the env gene of the vaccine strain were point-mutated to the wild-type sequence, respectively by an overlap PCR mutagenesis strategy. The infectivity, virulence, and pathogenesis of the constructed clones were investigated in vitro using a reverse transcriptase assay, an indirect immunofluorescence assay, observation of cytopathogenic effect, and virion observation as well as in vivo by inoculation of animals with the resulting infectious clones. The pathogenic symptoms in horses inoculated with mFD7-2-11 were more severe than those inoculated with mFD5-4-7, whereas no pathogenic symptoms were detected in animals inoculated with their parental clone pLGFD3 strain. The results indicate that the consensus mutation residues of the env region involved in this study play significant roles in the virulence and pathogenicity of EIAV. This will contribute to the elucidation of the attenuating and protective mechanisms of the Chinese EIAV vaccine.