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Solid organ transplantation has significantly prolonged the survival of patients with end-stage diseases. However, long-term use of immunosuppressants will increase the risk of post-transplantation diabetes mellitus (PTDM) in the recipients, thereby elevating the risk of infection, cardiovascular disease and death. In recent years, with persistent improvement of diagnostic criteria of PTDM, clinicians have deepened the understanding of this disease. Compared with type 2 diabetes mellitus, PTDM significantly differs in pathophysiological characteristics and clinical progression. Hence, different treatment strategies should be adopted. Early identification of risk factors of organ transplant recipients, early diagnosis and intervention are of significance for improving the quality of life of recipients, prolonging the survival of grafts and reducing the fatality of recipients. Therefore, the diagnosis, incidence and risk factors of PTDM were reviewed in this article, aiming to provide reference for clinicians to deliver prompt diagnosis and intervention for PTDM.
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ObjectiveTo investigate the Alzheimer-associated neurofilament protein （AD7c-NTP） in urine of middle-aged and elderly people and its correlation between common metabolites. MethodsA total of 1 150 middle-aged and elderly people who did their physical exmanination in the health examination center of the Sichuan Science City Hospital and the Third Hopital of Mianyang were recruited from March 2017 to March 2020. The level of urine AD7c-NTP were measured by enzyme-linked immunosorbent assay （ELISA）， and common metabolites in blood were measured by biochemical analyzer. Based on urine AD7c-NTP level ≤1.5 ng/mL， the objects was divided into normal group （n=956） and elevated group （n=194）. Thier demographic data and blood biochemical indicators were collected. ResultsThe urine AD7c-NTP level in middle-aged and elderly people was 0.60（0.30~1.20） ng/mL. The urine AD7c-NTP level was higher in women than that in men ［1.04（0.40~1.30） ng/mL vs. 0.84（0.30~1.00） ng/mL， Z=4.202， P˂0.01］. And the urine AD7c-NTP level was lower in the normal group than that in the elevated group ［0.50（0.30~0.90） ng/mL vs. 2.10（1.70~2.10） ng/mL， Z=22.035， P˂0.01］. The results of the univariate comparison showed that， the differences between the two groups in age （Z=6.545）， fasting glucose （Z=3.506）， blood uric acid （Z=2.574）， urea nitrogen （Z=2.891）， creatinine （Z=2.243）， total bilirubin （Z=3.936）， glutathione （Z=0.969）， total cholesterol （t=3.956） and low density lipoprotein （Z=-5.678） were were statistically significant （P˂0.05 or 0.01）. Spearman correlation analysis showed that， the urine AD7c-NTP level was positively correlated with age and the levels of urea nitrogen， glucose， total cholesterol and low density lipoprotein （r=0.177， 0.178， 0.171， 0.109， 0.149， P˂0.01）， and negatively correlated with the level of total bilirubin （r=-0.172， P˂0.01）. Conclusionthe urine AD7c-NTP level in middle-aged and elderly females was signifitcantly higher than in middle-aged and elderly males.The urine AD7c-NTP level of middle-aged and elderly people was positively correlated with age， urea nitrogen， glucose， total cholesterol and low density lipoprotein， and negatively correlated with total bilirubin.
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Since the 1970s， patients with chronic pancreatitis （CP） have benefited from total pancreatectomy with autologous islet cell transplantation （TPAIT）. With the continuous development of surgical techniques and perioperative management over the past few decades， there have been improvements in islet cell function， insulin independence rate， and the survival rate of patients. This article summarizes the preoperative indications for TPAIT， the development of surgical operations， postoperative management and monitoring， and prognosis， so as to help clinicians learn more about TPAIT.
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Objective To investigate the effects of adoptive reinfusion of regulatory T cell (Treg) on the recovery of islet function and graft survival time after islet allograft transplantation. Methods The diabetic model was established using C57BL/6 mice as recipients, and Balb/c mice were chosen as donors for islet allografts transplantation beneath the renal capsule. The recipient mice were divided into 3 groups and 3 mice in each group according to different processing Methods: Treg experiment group (Treg group, 1×106 Treg cells were injected via tail vein at 1 d before operation), positive control group [sirolimus (SRL) group, SRL at a dose of 300 μg/(kg·d) was intragastrically given every day from 1 d before operation] and blank control group (control group, an equivalent volume of normal saline was intragastrically given every day from 1 d before operation). Enzyme-linked immune absorbent assay (ELISA) was used to detect the changes of blood glucose and C-peptide in mice within 14 days after transplantation. In vivo imaging technique was used to dynamically monitor the survival of mice within 14 days after transplantation. Results In each group, the blood glucose levels at postoperative 3 d were significantly decreased compared with those before transplantation (all P < 0.001). At postoperative 1 d, the C-peptide levels showed an explosive rise to varying degree in each group. At postoperative 3 d, the C-peptide levels in each group were significantly higher than that before operation (all P < 0.001). At the end of the observation period at 14 d after operation, the C-peptide levels in the SRL and Treg groups were (427±50) pmol/L and (833±57) pmol/L, relatively higher than that in the control group. But the blood glucose levels were (14.5±0.5) mmol/L and (12.1±0.6) mmol/L, significantly lower than that in the control group (all P < 0.001). Compared with the SRL group, the explosive release amount of C-peptide was significantly lower, the declining trend was more remarkably stable, and the C-peptide level was considerably higher in the Treg group at the end of the observation period (all P < 0.001). At postoperative 14 d, the grafts were almost completely apoptotic in the control group, over 50% of the grafts survived in the SRL group, and over 80% of the grafts survived in the Treg group. Conclusions Adoptive reinfusion of Treg cells can effectively protect islet grafts, prolong the survival time of grafts, and maintain the normal levels of blood glucose and C-peptide in the recipient mice.
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Objective To explore the effects of Qa-1 and PD-L1 loaded artificial liposomal treatment in allograft rejection and its outcomes .Methods The extracellular domains of Qa-1 and PD-L1 were loaded on liposome surface by streptavidin-biotin system . Mixed lymphocyte reaction (MLR) was performed for measuring Qa-1/PD-L1 liposome biological function .Then liposome was co-transplanted with allo-islets via portal vein .The levels of blood glucose and C-peptide were detected daily after transplantation .Also hepatic lymphocytes after transplantation were isolated for determining the proportion of activated cells and signaling pathway changes .Results Artificial liposome could be easily loaded with biotinylated peptide and its diameter was between 50 to 500 nm . Qa-1/PD-L1 liposome could significantly suppress lymphocyte proliferation , activation and secretion of IFN-γ in MLR by an activation of SHP1/2 and an inhibition of Syk pathway .Qa-1/ PD-L1 liposomes could suppress the activation of hepatic lymphocytes in vivo by activating SHP1/2 ,protecting islet allografts and maintaining a normal level of blood glucose in recipients .Conclusions Qa-1/PD-L1 loaded liposome can effectively suppress allograft rejection and improve the outcomes of islet transplantation .
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Necrosis is a form of cell death, which is related to various serious diseases such as cardiovascular disease, cancer, and neurodegeneration. Necrosis-avid agents (NAAs) selectively accumulated in the necrotic tissues can be used for imaging and/or therapy of related diseases. The aim of this study was to preliminarily investigate necrosis avidity of I-evans blue (I-EB) and its mechanism. The biodistribution of I-EB at 24 h after intravenous administration showed that the radioactivity ratio of necrotic to viable tissue was 3.41 in the liver and 11.82 in the muscle as determined by counting in model rats. Autoradiography and histological staining displayed preferential uptake of I-EB in necrotic tissues. nuclear extracts from necrotic cells exhibited 82.3% of the uptake in nuclei at 15 min, as well as 79.2% of the uptake at 2 h after I-EB incubation. The DNA binding study demonstrated that evans blue (EB) has strong binding affinity with calf-thymus DNA (CT-DNA) (=5.08×10 L/(mol/L)). Furthermore, the accumulation of I-EB in necrotic muscle was efficiently blocked by an excess amount of unlabeled EB. In conclusion, I-EB can not only detect necrosis by binding the DNA released from necrotic cells, but also image necrotic tissues generated from the disease clinically.