Immune rejection following liver transplantation is a critical factor affecting long-term graft survival. While traditional immunosuppressive regimens based on calcineurin inhibitors are effective， they are often accompanied by long-term side effects， making the induction of immune tolerance an important goal. This article systematically reviews the mechanisms of immune rejection following liver transplantation and the limitations of current drugs， with a focus on the potential of mesenchymal stem cells （MSCs） as a novel strategy for inducing immune tolerance. Preliminary clinical trials have confirmed that MSC infusion has a favorable safety profile and shows an immunomodulatory effect； however， there are still multiple challenges regarding the timing of infusion， cell source， dosage， and synergy with conventional regimens. Large-scale clinical trials are needed in the future to further validate their long-term efficacy and safety， and MSC therapy is expected to become a new direction for immune management in liver transplantation.

In recent years,as the survival time of liver transplant recipients continues to increase,serious complications after transplantation,including diabetes,which affects the long-term survival of patients,have attracted more and more attention.Diabetes after liver transplantation can increase the risk of infection and cardiovascular disease,which in turn affects the survival rate of grafts and patients,and therefore,identification and intervention for high-risk populations are of great importance for improving the prognosis of patients.This article reviews the risk factors for diabetes after liver transplantation,in order to deepen the understanding of diabetes after liver transplantation and provide a theoretical basis for disease prevention and treatment.

Objective This study was to investigate the effects of Ginseng Astragalus Tumor Suppressor Formula combined with cisplatin on relevant immune genes and immune functions in mice modeled with hepatocellular carcinoma based on bioinformatics research.Methods Gene expression profiles and clinical data of hepatocellular carcinoma patients were downloaded from TCGA and GEO databases and screened for immune-expressed genes by taking intersections with immune-related genes downloaded from ImmPort database.Immune-related gene pair coefficients(IRGPI)were calculated to construct IRGP prognostic models.The optimal cut-off value of IRGPI for 1-year overall survival of hepatocellular carcinoma patients was determined based on ROC curve analysis,and hepatocellular carcinoma patients were divided into high and low immune risk groups,and the survival status of patients in the two groups was analyzed using the Kaplan-Meier method and the Log-Rank test.Then,we screened the active ingredients and gene targets of Ginseng Astragali Tumor Suppressor Formula for the treatment of hepatocellular carcinoma by network pharmacology,and obtained the intersection genes between Ginseng Astragali Tumor Suppressor Formula and disease,and then extracted the intersection of hepatocellular carcinoma-related immune genes and the intersection genes between Ginseng Astragali Tumor Suppressor Formula and disease through the"VennDiagram"software,and verified it through the animal model.The effects of Astragalus tumor-suppressing formula combined with cisplatin on the immunity genes and immune functions in the tumor tissues of mice with hepatocellular carcinoma were verified in animal models.Results Among 2483 relevant immune genes,84 pairs of immune-related genes were significantly associated with OS in the experimental group(P<0.001),and among the patients categorized into high and low immune risk groups by cut-off value-0.258,the overall survival rate of the high immune risk group was significantly lower than that of the low immune risk group(P<0.001).Univariate Cox analysis showed that IRGP model risk values and clinical characteristics of tumor T-staging had an impact on prognosis.Multifactorial Cox analysis showed that IRGP model risk value and tumor T-stage could be used as independent prognostic factors.266 genes intersecting with hepatocellular carcinoma were screened by network pharmacology technique for Ginseng Astragalus Tumor Suppressor Formula,and further 8 genes were obtained by taking the intersection with 84 pairs of immune-related genes.The experimental results showed that compared with the model group,the tumor mass of mice in each treatment group decreased(P<0.05);the spleen index and thymus index of mice increased(P<0.05);the CD4+/CD8+ratio in serum and spleen tissues of mice decreased;ICAM1,FABP5,IGF2,CDK4,NR1,ADRB2,AR,NR3C2 in tumor tissue of mice mRNA expression were all decreased(P<0.05),and the therapeutic effect of the combined group was significant(P<0.01).Conclusion This study predicted the key immune genes related to hepatocellular carcinoma as well as the prognostic analysis of immune-related genes,and the experimental study verified that Ginseng and Astragalus Tumor Suppressor Formula could effectively reduce the expression of related immune genes in tumor tissues,and improve the proportion of related immune cells in the splenic tissues of mice with hepatocellular carcinoma model as well as improve the immune function of mice.

In recent years,as the survival time of liver transplant recipients continues to increase,serious complications after transplantation,including diabetes,which affects the long-term survival of patients,have attracted more and more attention.Diabetes after liver transplantation can increase the risk of infection and cardiovascular disease,which in turn affects the survival rate of grafts and patients,and therefore,identification and intervention for high-risk populations are of great importance for improving the prognosis of patients.This article reviews the risk factors for diabetes after liver transplantation,in order to deepen the understanding of diabetes after liver transplantation and provide a theoretical basis for disease prevention and treatment.

Objective This study was to investigate the effects of Ginseng Astragalus Tumor Suppressor Formula combined with cisplatin on relevant immune genes and immune functions in mice modeled with hepatocellular carcinoma based on bioinformatics research.Methods Gene expression profiles and clinical data of hepatocellular carcinoma patients were downloaded from TCGA and GEO databases and screened for immune-expressed genes by taking intersections with immune-related genes downloaded from ImmPort database.Immune-related gene pair coefficients(IRGPI)were calculated to construct IRGP prognostic models.The optimal cut-off value of IRGPI for 1-year overall survival of hepatocellular carcinoma patients was determined based on ROC curve analysis,and hepatocellular carcinoma patients were divided into high and low immune risk groups,and the survival status of patients in the two groups was analyzed using the Kaplan-Meier method and the Log-Rank test.Then,we screened the active ingredients and gene targets of Ginseng Astragali Tumor Suppressor Formula for the treatment of hepatocellular carcinoma by network pharmacology,and obtained the intersection genes between Ginseng Astragali Tumor Suppressor Formula and disease,and then extracted the intersection of hepatocellular carcinoma-related immune genes and the intersection genes between Ginseng Astragali Tumor Suppressor Formula and disease through the"VennDiagram"software,and verified it through the animal model.The effects of Astragalus tumor-suppressing formula combined with cisplatin on the immunity genes and immune functions in the tumor tissues of mice with hepatocellular carcinoma were verified in animal models.Results Among 2483 relevant immune genes,84 pairs of immune-related genes were significantly associated with OS in the experimental group(P<0.001),and among the patients categorized into high and low immune risk groups by cut-off value-0.258,the overall survival rate of the high immune risk group was significantly lower than that of the low immune risk group(P<0.001).Univariate Cox analysis showed that IRGP model risk values and clinical characteristics of tumor T-staging had an impact on prognosis.Multifactorial Cox analysis showed that IRGP model risk value and tumor T-stage could be used as independent prognostic factors.266 genes intersecting with hepatocellular carcinoma were screened by network pharmacology technique for Ginseng Astragalus Tumor Suppressor Formula,and further 8 genes were obtained by taking the intersection with 84 pairs of immune-related genes.The experimental results showed that compared with the model group,the tumor mass of mice in each treatment group decreased(P<0.05);the spleen index and thymus index of mice increased(P<0.05);the CD4+/CD8+ratio in serum and spleen tissues of mice decreased;ICAM1,FABP5,IGF2,CDK4,NR1,ADRB2,AR,NR3C2 in tumor tissue of mice mRNA expression were all decreased(P<0.05),and the therapeutic effect of the combined group was significant(P<0.01).Conclusion This study predicted the key immune genes related to hepatocellular carcinoma as well as the prognostic analysis of immune-related genes,and the experimental study verified that Ginseng and Astragalus Tumor Suppressor Formula could effectively reduce the expression of related immune genes in tumor tissues,and improve the proportion of related immune cells in the splenic tissues of mice with hepatocellular carcinoma model as well as improve the immune function of mice.

Objective:To explore the effects of IFN-γ on IL-8 secretion by human liver cancer cells and the impact on their malignant biological functions in vitro. Methods:HuH7 and Hep3B cells were treated with different concentrations of IFN-γ for 24 or 48 h. Changes in the cellular activity, IL-8 secretion, and the proportion of CD133 + liver cancer stem cells were evaluated using CCK8 kit and flow cytometry. Western blot was used to detect the effects of IFN-γ on the expression of several molecules such as phosphorylated protein kinase B (p-Akt), phosphorylated c-Jun N-terminal kinase (p-JNK), vimentin, and E-cadherin in the liver cancer cells. Effects of IFN-γ with or without IL-8 on the migration of liver cancer cells were detected by transwell assay. Additionally, effects of IFN-γ combined with IL-8 or IL-8 receptor inhibitor repertaxin on the differentiation of liver cancer stem cells were detected by flow cytometry. One-way analysis of variance and Tukey-Kramer test were used for statistical analysis. Results:HuH7 and Hep3B cells secreted significantly higher levels of IL-8 than normal hepatocytes LO2 ( P<0.01) and high expression level of IL-8 gene ( CXCL8) was closely correlated with the expression levels of vimentin gene ( VIMENTIN), CD133 gene ( PRCM1), PD-L1 gene ( CD274), PD-1 gene ( PDCD1), and CD163 gene ( CD163), as well as the poor prognosis of liver cancer patients ( P<0.01). IFN-γ (1-100 ng/ml) had no significant effect on the proliferative activity of HuH7 and Hep3B cells ( P>0.05), but could significantly inhibit IL-8 secretion, cell migration, CD133 + liver cancer stem cell differentiation and suspension tumor sphere formation through the Akt and JNK pathways ( P<0.01). IFN-γ combined with IL-8 could significantly reversed the inhibitory effects of IFN-γ on liver cancer cell migration, stem cell differentiation, and suspension tumor sphere formation ( P<0.01). IFN-γ in combination with repertaxin could synergistically inhibited the differentiation of CD133 + liver cancer stem cells ( P<0.01). Conclusion:IFN-γ inhibits the differentiation and migration of human liver cancer cells through the Akt/JNK-IL-8 signaling pathway, providing a new strategy for future clinical immunotherapy of liver cancer.

Objective:To establish the reference interval of 12 types of cytokines(IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,IFN-γ,IFN-α,TNF-α)in adult plasma based on multiple microsphere flow immunofluorescence(MBFFI).Methods:A total of 140 healthy adult patients who were examined at Xuzhou Central Hospital between January 2022 and December 2023 were included in the study.Plasma cytokine levels were detected and reference intervals were established by the flow cytometer and the assay kits produced by Qingdao Raisecare Biotechnology Co.,Ltd and Jiangsu BioPredia Biotechnology Co.,Ltd.Results:All of the cytokines exhibited a non-normal distribution,and there was a discrepancy in the 95％reference interval between the two re-agents.The reference intervals for the 12 cytokine kits produced by Qingdao Raisecare Biotechnology Co.,Ltd.were as follows:IFN-α:<4.91 pg/ml,IL-12 p70:<1.95 pg/ml,IL-5:<12.72 pg/ml,IL-8:<60.68 pg/ml,IL-1β:<27.67 pg/ml,IL-2:<5.01 pg/ml,IL-4:<1.22 pg/ml,IL-6:<6.11 pg/ml,TNF-α:<2.92 pg/ml,IL-17:<10.27 pg/ml,IL-10:<6.88 pg/ml,IFN-γ:<17.68 pg/ml.The reference intervals of the 12 cytokines produced by Jiangsu BioPredia Biotechnology Co.,Ltd.were as follows:IFN-α:<4.05 pg/ml,IL-12 p70:<7.33 pg/ml,IL-5:<7.80 pg/ml,IL-8:<13.24 pg/ml,IL-1β:<19.24 pg/ml,IL-2:<2.42 pg/ml,IL-4:<0.99 pg/ml,IL-6:<2.10 pg/ml,TNF-α:<0.87 pg/ml,IL-17:<1.42 pg/ml,IL-10:<1.10 pg/ml,IFN-γ:<1.34 pg/ml.Conclusion:In this study,the ref-erence range of two reagents for the detection of 12 kinds of cytokines in plasma of healthy adults is established by MBFFI,which pro-vides a valuable reference for the diagnosis and treatment of clinical-related diseases.

Objective:To explore the effects of IFN-γ on IL-8 secretion by human liver cancer cells and the impact on their malignant biological functions in vitro. Methods:HuH7 and Hep3B cells were treated with different concentrations of IFN-γ for 24 or 48 h. Changes in the cellular activity, IL-8 secretion, and the proportion of CD133 + liver cancer stem cells were evaluated using CCK8 kit and flow cytometry. Western blot was used to detect the effects of IFN-γ on the expression of several molecules such as phosphorylated protein kinase B (p-Akt), phosphorylated c-Jun N-terminal kinase (p-JNK), vimentin, and E-cadherin in the liver cancer cells. Effects of IFN-γ with or without IL-8 on the migration of liver cancer cells were detected by transwell assay. Additionally, effects of IFN-γ combined with IL-8 or IL-8 receptor inhibitor repertaxin on the differentiation of liver cancer stem cells were detected by flow cytometry. One-way analysis of variance and Tukey-Kramer test were used for statistical analysis. Results:HuH7 and Hep3B cells secreted significantly higher levels of IL-8 than normal hepatocytes LO2 ( P<0.01) and high expression level of IL-8 gene ( CXCL8) was closely correlated with the expression levels of vimentin gene ( VIMENTIN), CD133 gene ( PRCM1), PD-L1 gene ( CD274), PD-1 gene ( PDCD1), and CD163 gene ( CD163), as well as the poor prognosis of liver cancer patients ( P<0.01). IFN-γ (1-100 ng/ml) had no significant effect on the proliferative activity of HuH7 and Hep3B cells ( P>0.05), but could significantly inhibit IL-8 secretion, cell migration, CD133 + liver cancer stem cell differentiation and suspension tumor sphere formation through the Akt and JNK pathways ( P<0.01). IFN-γ combined with IL-8 could significantly reversed the inhibitory effects of IFN-γ on liver cancer cell migration, stem cell differentiation, and suspension tumor sphere formation ( P<0.01). IFN-γ in combination with repertaxin could synergistically inhibited the differentiation of CD133 + liver cancer stem cells ( P<0.01). Conclusion:IFN-γ inhibits the differentiation and migration of human liver cancer cells through the Akt/JNK-IL-8 signaling pathway, providing a new strategy for future clinical immunotherapy of liver cancer.

Objective:To establish the reference interval of 12 types of cytokines(IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,IFN-γ,IFN-α,TNF-α)in adult plasma based on multiple microsphere flow immunofluorescence(MBFFI).Methods:A total of 140 healthy adult patients who were examined at Xuzhou Central Hospital between January 2022 and December 2023 were included in the study.Plasma cytokine levels were detected and reference intervals were established by the flow cytometer and the assay kits produced by Qingdao Raisecare Biotechnology Co.,Ltd and Jiangsu BioPredia Biotechnology Co.,Ltd.Results:All of the cytokines exhibited a non-normal distribution,and there was a discrepancy in the 95％reference interval between the two re-agents.The reference intervals for the 12 cytokine kits produced by Qingdao Raisecare Biotechnology Co.,Ltd.were as follows:IFN-α:<4.91 pg/ml,IL-12 p70:<1.95 pg/ml,IL-5:<12.72 pg/ml,IL-8:<60.68 pg/ml,IL-1β:<27.67 pg/ml,IL-2:<5.01 pg/ml,IL-4:<1.22 pg/ml,IL-6:<6.11 pg/ml,TNF-α:<2.92 pg/ml,IL-17:<10.27 pg/ml,IL-10:<6.88 pg/ml,IFN-γ:<17.68 pg/ml.The reference intervals of the 12 cytokines produced by Jiangsu BioPredia Biotechnology Co.,Ltd.were as follows:IFN-α:<4.05 pg/ml,IL-12 p70:<7.33 pg/ml,IL-5:<7.80 pg/ml,IL-8:<13.24 pg/ml,IL-1β:<19.24 pg/ml,IL-2:<2.42 pg/ml,IL-4:<0.99 pg/ml,IL-6:<2.10 pg/ml,TNF-α:<0.87 pg/ml,IL-17:<1.42 pg/ml,IL-10:<1.10 pg/ml,IFN-γ:<1.34 pg/ml.Conclusion:In this study,the ref-erence range of two reagents for the detection of 12 kinds of cytokines in plasma of healthy adults is established by MBFFI,which pro-vides a valuable reference for the diagnosis and treatment of clinical-related diseases.

With the population ageing, the number of elderly with noncommunicable diseases and functional disabilities is increasing. The assistive technology can improve the ability of older adults for daily living activities and reduce dependence on caregivers to facilitate home-based care for the elderly. However, the provision of assistive technology service in China is still in the early stage and lacks implementable model. This article introduces international experiences on the delivery of assistive technology service, and discusses the status quo and problems of assistive technology service in China, to provide insights for promoting assistive technology service in the primary health care.