Analysis of key genes and targeted protection methods affecting the survival of human islets / 器官移植

Objective To identify the key genes and targeted protection methods affecting the survival of human islets. Methods Using bioinformatics method, the gene expression profile (GSE53454) was selected through screening and comparison from Gene Expression Omnibus(GEO) database. GEO2R tool was employed to screen the differentially expressed gene(DEG) between the human islets exposed (exposure group) and non-exposed (non-exposure group) to interleukin (IL)-1β and interferon (IFN)-γ for 24, 48 and 72 h, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by DAVID. Protein-protein interaction (PPI) network was constructed by STRING and Cytoscape apps. Results A total of 69 up-regulated DEGs and 2 down-regulated DEGs were identified. GO analysis showed that during the biological process, DEGs were enriched in the aspects of virus defense and inflammatory response. In cellular components, DEGs were significantly enriched in extracellular space, outside plasma membrane and extracellular regions. Regarding molecular functions, DEGs were significantly enriched in chemokine activity and cytokine activity. KEGG analysis revealed that DEGs were mainly enriched in multiple signaling pathways, such as cytokine-cytokine receptor interaction, virus protein-cytokine and cytokine-receptor interaction, etc. Ten key genes (STAT1, CXCL10, IRF1, IL6, CXCL9, CCL5, CXCL11, ISG15, CD274, IFIT3) with high connectivity were selected by STRING analysis, all of which were significantly up-regulated in human islets exposed to IL-1β and IFN-γ. Six genes (STAT1, CXCL10, CXCL9, CXCL11, CCL5, IL6) were screened by KEGG enrichment analysis, mainly in Toll-like receptor signaling pathway. Conclusions STAT1, CXCL10, CXCL9, CXCL11, CCL5 and IL6 are the key genes affecting the survival of human islets, which are mainly enriched in Toll-like receptor signaling pathway and act as important targets for islet protection.

Research progress on islet protection and functional maintenance / 器官移植

Islet transplantation is a promising treatment of diabetes mellitus and its complications. Nevertheless, dysfunction post-transplantation, rejection and shortage of donors are the bottleneck issues in the field of islet transplantation. Optimizing the preservation method of pancreas plays a positive role in obtaining a sufficient quantity of effective islets and maintaining their functions. During the culture stage, anti-rejection and anti-apoptosis treatment of islets, including mesenchymal stem cell (MSC), MSC-derived exosomes, anti-apoptosis drugs and gene modification, may become major approaches for islet protection and functional maintenance in clinical islet transplantation. Use of anti-instant blood-mediated inflammatory reaction (IBMIR) drugs after islet transplantation also plays a critical role in protecting islet function. In this article, the whole process from islet preparation to islet transplantation was illustrated, and relevant strategies of islet protection and functional maintenance were reviewed, aiming to provide reference for improving the quality of donors to compensate for the shortage of absolute quantity of donors and elevating the efficiency of islet transplantation.

In vitro research of mesenchymal stem cell-coated human islets to alleviate instant blood-mediated inflammatory reaction / 器官移植

Objective To evaluate the effect of mesenchymal stem cell (MSC) coated-islets on instant blood-mediated inflammatory reaction (IBMIR) after islet transplantation. Methods MSC labeled with tracer and human islets were placed into an ultra-low adsorption cell culture dish, shaken and mixed twice at an interval of 0.5 h, and then incubated at 37 ℃ and 5% CO2 for 24 h to obtain MSC-coated islets. The coating effect of MSC and in vitro function of the islets were assessed. A blood circulation tube-shaped model was established in vitro. In the blank control group, 0.2 mL of islet culture solution was added. In the islet group, 800 islet equivalent quantity (IEQ) of uncoated islets were supplemented. In the MSC-coated islets group, 800 IEQ of MSC-coated islets were added, and circulated for 60 min at 37 ℃. A portion of 0.5 mL blood sample was taken for routine blood test at 0, 30 and 60 min, respectively. After 60 min circulation, the blood sample was filtered with a 70 μm filter to collect plasma, blood clots and islets. Blood clots and islets were subject to hematoxylin-eosin (HE) staining and immunohistochemical staining. Morphological changes and the aggregation of CD11b-positive cells surrounding the islets were observed. The contents of plasma thrombin-antithrombin complex (TAT), tissue factor (TF), C3a, C5b-9, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1 and IL-8 were determined by enzyme-linked immune absorbent assay. Results After 24 h co-incubation, the islets were coated by MSC, with a coating degree of approximately 80%. In the islet and MSC-coated islet group, a large quantity of neutrophils and monocytes were observed surrounding the blood clots and islets, and the quantity of CD11b-positive cells in the MSC-coated islet group was less compared with that in the islet group. After co-incubation with the whole blood for 0, 30 and 60 min, the quantity of platelets, neutrophils and monocytes was declined in the MSC-coated and islet groups, and gradually decreased over time. Compared with the blank control group, the quantity of platelets, monocytes and neutrophils was lower, whereas the TF content was higher in the MSC-coated islet group. Compared with the islet group, the quantity of platelets, monocytes and neutrophils was higher, whereas the TAT and TF contents were less in the MSC-coated islet group, the differences were statistically significant (all P < 0.05). Compared with the blank control group, the expression levels of C3a, C5b-9, IL-6, TNF-α and IL-8 were up-regulated in the MSC-coated islet group. Compared with the islet group, the expression levels of C3a, C5b-9, IL-1β, IL-6, TNF-α, IL-8 and MCP-1 were down-regulated in the MSC-coated islet group, and the differences were statistically significant (all P < 0.05). Conclusions MSC-coated islets may reduce the exposure of islet TF in the blood and prevent the incidence of IBMIR during the coagulation response stage, thereby mitigating the injury and loss of islet allograft in the early stage of islet transplantation.

Therapeutic strategy for instant blood-mediated inflammatory reaction after islet transplantation / 器官移植

As an effective procedure for type 1 diabetes mellitus and end-stage type 2 diabetes mellitus, islet transplantation could enable those patients to obtain proper control of blood glucose levels. Instant blood-mediated inflammatory reaction (IBMIR) is a nonspecific inflammation during early stage after islet transplantation. After IBMIR occurs, coagulation cascade, complement system activation and inflammatory cell aggregation may be immediately provoked, leading to loss of a large quantity of transplant islets, which severely affects clinical efficacy of islet transplantation. How to alleviate the islet damage caused by IBMIR is a hot topic in islet transplantation. Heparin and etanercept, an inhibitor of tumor necrosis factor-α, are recommended as drugs for treating IBMIR following islet transplantation. Recent studies have demonstrated that multiple approaches and drugs may be adopted to mitigate the damage caused by IBMIR to the islets. In this article, the findings in clinical and preclinical researches were reviewed, aiming to provide reference for the management of IBMIR after islet transplantation.

Research progress on optimization strategies for microencapsulated islet transplantation / 器官移植

Islet transplantation is one of the effective therapies for diabetes mellitus. Nevertheless, multiple issues still exist, such as shortage of donors and adverse reactions caused by long-term use of immunosuppressants, which limit the islet survival post-transplantation. Microencapsulated islet transplantation may overcome these difficulties to certain extent, whereas many factors, such as the destruction of immune isolation microenvironment within the microcapsules and insufficient supply of oxygen and nutrients, constrain the application of microencapsulated islet transplantation in clinical practice. In recent years, how to enhance the effect of microencapsulated islet transplantation has been gradually studied. The application of stem cells in microencapsulated islet transplantation has steadily become a research hot spot. Therefore, the optimizing strategies for microencapsulated islet transplantation and the application of stem cells in microencapsulated islet transplantation were reviewed, and the potential improvement techniques of microencapsulated islet transplantation were investigated in this article, aiming to provide reference for further clinical application of microencapsulated islet transplantation.

Mechanism of compound Fufangteng mixture-containing serum in promoting proliferation of bone marrow mesenchymal stem cell / 器官移植

Objective To investigate the effect of compound Fufangteng mixture-containing serum on the proliferation of bone marrow mesenchymal stem cell (BMSC) and its mechanism. Methods Rat BMSC were isolated, cultured and purified in vitro by direct adherence method. Cell morphology was observed. Surface markers were identified by flow cytometry. The rats were treated with compound Fufangteng mixture at a dose of 3 mL/(kg·d) by gavage for 14 d, and then the drug-containing serum was collected. BMSC were divided into the blank control group, drug-containing serum group, Notch1 small interfering ribonucleic acid (siRNA) group and Notch1 siRNA+drug-containing serum group. The proliferation rate of BMSC was detected and the relative expression levels of Notch1 signaling pathway-associated messenger ribonucleic acid (mRNA) and proteins were measured in each group. Results Microscopic observation showed that the first generation BMSC were seen in the long spindle shape, and grown in the parallel or spiral pattern. The third generation BMSC positively expressed CD90 and CD44, whereas were negative for CD45. Compared with the blank control group, the proliferation rate of BMSC in the drug-containing serum group and Notch1 siRNA+ drug-containing serum group was significantly increased, whereas that of BMSC was significantly decreased in the Notch1 siRNA group (all P < 0.05). Compared with the Notch1 siRNA group, the proliferation rate of BMSC was significantly increased in the Notch1 siRNA+drug-containing serum group (P < 0.05). Compared with the blank control group, the relative expression levels of Hey1 and Delta-like ligand (DLL)1 mRNA and proteins were significantly up-regulated in the drug-containing serum group, whereas those were significantly down-regulated in the Notch1 siRNA group and Notch1 siRNA+drug-containing serum group (all P < 0.05). Compared with the Notch1 siRNA group, the relative expression levels of Hey1 and DLL1 mRNA and proteins were significantly up-regulated in the Notch1 siRNA+drug-containing serum group (all P < 0.05). Conclusions Compound Fufangteng mixture-containing serum may promote the proliferation of rat BMSC, and its mechanism is probably associated with the activation of Notch1 signaling pathway.

Irreversible electroporation ablation of tumor: an analysis of perioperative complications / 介入放射学杂志

Objective To summarize and analyze the perioperative complications of irreversible electroporation (IRE) ablation in treating tumors at different locations and to discuss their managements. Methods A total of 200 patients with tumors, including pancreatic tumor (n=71), liver tumor (n=64) and other tumors (n =65), were enrolled in this study. All patients received IRE ablation treatment. The perioperative complications were recorded and the data were statistically analyzed. The causes of severe complications and the treatment of complications were discussed. Results None of the patients died during the course of IRE ablation procedure. Severe postoperative complications occurred in the patients with pancreatic tumor or liver tumor, including duodenal artery bleeding in 3 patients with pancreatic tumor, which occurred at 10 days, 11 days and 15 days after IRE ablation respectively, and gastrointestinal bleeding (n =1) and biliary septic shock (n=1) in 2 patients with liver tumor, which occurred at 9 days after IRE ablation, the clinical symptoms were controlled after interventional embolization and/or vascular ligation together with anti-infective therapy. All minor complications were relieved after symptomatic treatment within 14 days. Conclusion IRE ablation has less systemic inflammatory response, and both the intraoperative and postoperative adverse reactions can be easily controlled, besides, IRE ablation has higher clinical safety. Although IRE ablation procedure may damage the internal or peripheral vessels of the pancreatic tumor, this severe complications can be effectively avoided if proper measures are adopted based on the causes of complications. (J Intervent Radiol, 2018, 27: 223-227)

Progress of research on the minimally invasive treatment of bone metastases / 国际肿瘤学杂志

In recent years,minimally invasive techniques,such as percutaneous cementoplasty,percutaneous cryoablation,magnetic-resonance-guided focused ultrasound surgery,radiofrequency ablation,microwave ablation,radioactive particle implantation,transcatheter arterial embolization and irreversible electroporation et al,play more and more important roles in the treatments of bone metastasis.Compare with traditional therapies like radiotherapy,drugs and surgery,the better efficacy and security of minimally invasive techniques have been demonstrated by voluminous animal experiments and clinical trials.However,the clinical application of minimally invasive techniques have still some controversial issues.

Progress on Minimally Invasive Treatment of Localized Prostate Cancer / 中国微创外科杂志

[Summary] Radical prostatectomy, external beam radiation and active surveillance are the main treatments for localized prostate cancer. However, many patients are difficult to accept the psychological burden of active surveillance and the distress caused by potential side effects of radical therapy, including incontinence and erectile dysfunction, which make them limited. With the development of minimally invasive techniques, such as brachytherapy, cryoablation, high-intensity focused ultrasound, photodynamic therapy, and irreversible electroporation, novel procedures are playing an increasingly important role in the treatment of localized prostate cancer with their effective, minimally invasive, and safe advantages. This article mainly reviewed the above several minimally invasive treatment methods.

Research progress in targeted immunotherapy combined with ra-diotherapy for stageⅢ/Ⅳmelanomas / 中国肿瘤临床

Melanoma is the most aggressive and lethal malignant tumor in skin cancers. Operation resection is used to treat stageⅠ/Ⅱmelanomas, but traditional operation, chemotherapy, and radiotherapy inflicts adverse effects on late-stage melanomas. StageⅢ/Ⅳmelanomas are some of the most ineffectively treated tumors with poor prognosis. As a cancer treatment, targeted immunotherapy in-hibits negative regulatory factors and enhances systemic anti-tumor immune effects. Radiotherapy not only kills tumor cells, but also en-hances systemic immune responses. Recent studies showed that targeted immunotherapy combined with radiotherapy can promote con-trol on local and distant tumors and prolong overall survival. The synergistic effects of these two therapies are superior to a single thera-py. This review summarized the progress on these research fields.

A comparison of dual- and triple-freeze protocols for liver cryoablation in a Tibet pig / 中华肝胆外科杂志

Objective This study compares a dual-freeze protocol with a triple freeze protocol for hepatic cryoablation in the Tibetan pig model.Method Cryoablation with a dual-(10-5-10-5 min)and triple-freeze (5-5-5-5-10-5 min) protocol for the normal livers of 9 Tibet pigs was performed under exposed operation.Temperature changes of cryoprobes and diameter changes of iceballs were measured during the ablation,and seven days later the pathological changes of cryozones were reviewed and the surface and depth cryolesions were measured.Results Compared with cryoablation with two freeze-thaw cycles,there was a greater iceball diameter for cryoablation by three freeze-thaw cycles.Also,seven days after cryosurgery,there were similar surface and deep cryolesions in dual-and triple-freeze protocols.Pathologically,the triple freezing protocol was associated with a longer zone of complete necrosis.Conclusions With the same freezing time (20 min),the triple-freeze protocol may become a more powerful liver-ablation method in cryosurgical application.