Objective To study the mechanism of immune hyporesponsiveness of allograft rejection induced by transfusion nonpufsed allopeptide syngeneic immature dendritic cell (imDC) generated from recipient bone marrow progenitors and to explore a possible strategy for liver allograft protection in clinic. Methods Forty experimental rats were randomly divided into 4 group: control group, cyclosporine A (CsA) group, mature DC (mDC) group and imDC group. In control group, Wistar rats only received liver transplantation. In CsA group, Wistar rats underwent liver transplantation plus CsA treatment 〔10 mg/（kg·d)〕. In mDC group, recipient-derived mDC 1×106 were infused intravenously through the penile vein to Wistar rats. In imDC group, ImDC with the dose of 1×106 were injected into Wistar rats via the dorsum vein of penile. In each group, five recipients were killed on the 10th day after transplantation, the other five recipients were left to observe survival time. The levels of ALT, AST, TBIL, IL-2, IFN-γ, IL-4 and IL-10 were detected. The acute rejection and the expression of FasL/Fas in the grafts were detected by HE and immunohistochemical staining. Western blot was used to detect Scurfin protein expression of CD4+ CD25+ T cells. Results The median survival time of the liver allografts in CsA group and imDC group were significantly longer than that in control group and mDC group ( P ＜ 0.05). The levels of ALT and TBIL in control group and mDC group were significantly higher than those in CsA group and imDC group ( P ＜ 0.05). Compared with CsA group and imDC group, the levels of IL-2 and IFN-γ were higher but the levels of IL-4 and IL-10 were lower in control group and mDC group ( P ＜ 0.01). Slightly or no rejection reaction was found in CsA group and imDC group ( P ＜ 0.05). The Scurfin protein expressions of CD4+ CD25+ T cells of imDC group were significantly higher than those of other three groups. Conclusion Application of nonpufsed allopeptide syngeneic recipient-derived imDC is an effective way to induce immune hyporesponsiveness by blocking indirect recognition in rat liver transplantation model. Survival span is significantly prolonged by its protective effect. The mechanism of immune hyporesponsiveness induced by imDC transfusion might be involved in some aspects: T cell apoptosis, immune deviation of Thl/Th2 cytokine net and inhibition of T lymphocytes responsiveness by regulatory T cells.
ObjectiveTo analyze and forecast trends in the burden of liver cancer in Yunnan Province, thereby providing a basis for the formulation of liver cancer prevention and control strategies. MethodsData on incidence, mortality, and disability-adjusted life year (DALY) for liver cancer from the Global Burden of Diseases 2021 study in Yunnan Province were extracted. The Joinpoint regression model was used to analyze trends in incidence rate and age-standardized incidence rate (ASIR), mortality rate and age-standardized mortality rate (ASMR), DALY rate and age-standardized DALY rate. A Bayesian age-period-cohort model was used to project the trends in ASIR and ASMR from 2022–2030. ResultsFrom 1990 to 2021, the incidence, mortality, and DALY rates for liver cancer in Yunnan Province increased from 5.07/100 000, 5.00/100 000, and 181.52/100 000 to 11.59/100 000, 10.39/100 000, and 316.94/100 000, respectively, with average annual percentage changes of 2.73% [95%CI (2.68%, 2.77%), P<0.001], 2.45% [95%CI (2.34%, 2.56%), P<0.001], and 1.86% [95%CI (1.77%, 1.96%), P<0.001]. ASIR, ASMR, and age-standardized DALY rate also increased from 7.20/100 000, 7.37/100 000, and 234.34/100 000 to 8.84/100 000, 8.06/100 000, and 239.26/100 000. Average annual percentage changes were 0.68% [95%CI (0.65%, 0.71%), P<0.001], 0.30% [95%CI (0.19%, 0.40%), P<0.001], and 0.11% [95%CI (0.00%, 0.22%), P=0.046]. In 2021, the incidence, mortality, and DALY burden of liver cancer among male in Yunnan Province were all higher than those among female. Incidence and mortality rates increased steadily with age, peaking in the ≥85 age group, while the number of new cases, deaths, and DALYs followed a pattern of initially rising and then declining. It was projected that by 2030, the annual number of new cases and deaths from liver cancer in Yunnan Province will rise to 6 100 and 5 100, respectively, while ASIR and ASMR will decrease to 8.72/100 000 [95%CI (5.46/100 000, 11.97/100 000)] and 6.82/100 000 [95%CI (1.74/100 000, 11.91/100 000)], respectively. ConclusionsThe burden of liver cancer in Yunnan Province continued to increase from 1990 to 2021, with men bearing a heavier burden. In its future efforts to prevent and control liver cancer, Yunnan Province should consolidate primary prevention measures while precisely targeting middle-aged and elderly populations for liver cancer screening, and examine the synergistic carcinogenic effects of emerging risk factors such as metabolic liver disease.