Liver graft injury caused by de novo donor-specific HLA antibodies in pediatric liver transplant recipients with low, moderate, and high immunologic risk.

BACKGROUND: This study investigated the association between different risk levels of de novo donor-specific anti-human leukocyte antigen antibodies (dnDSAs) and liver graft injury after liver transplantation in pediatric patients. METHODS: This retrospective cohort study enrolled 130 patients after liver transplantation. Subjects were divided into the following 4 groups according to the mean fluorescence intensity (MFI) of dnDSAs: high risk group(MFI ≥10,000), medium risk group(4000 ≤ MFI <10,000), low risk group(500 ≤ MFI <4000), and negative group(<500). Liver function indices were examined along with liver puncture biopsy，and the relationship between dnDSA risk level and liver injury after transplantation was assessed. RESULTS: Pediatric liver transplant recipients showed significant differences in liver function (ALT, AST, GGT and Bilirubin) according to dnDSA risk level (P < 0.05), and no differences in cumulative incidences of rejection (P = 0.413) and liver fibrosis (P = 0.978) were observed among the number of dnDSAs group. There were differences in the cumulative incidences of antibody-mediated rejection (AMR) (P = 0.001) and T cell-mediated rejection （TCMR） (P = 0.003) across risk groups. The cumulative incidences of TCMR and liver fibrosis (P = 0.0001) were higher in the low-risk group than in the other 3 groups. There were no differences in graft survival rate (P = 0.846) across risk groups. CONCLUSION: DnDSAs in pediatric liver transplant recipients are associated with liver transplant rejection and fibrosis. The level of dnDSAs in low risk group should not be disregarded. Routine detection of dnDSAs has clinical utility for noninvasive risk stratification in this population.

Levels of angiotensin II type-1 receptor antibodies and endothelin-1 type-A receptor antibodies correlate with antibody-mediated rejection and poor graft function in kidney-transplantation patients.

OBJECTIVE: Angiotensin II type-1 receptor antibodies (AT1R-Ab) and endothelin-1 type-A receptor antibodies (ETAR-Ab) are non-human leukocyte antigen (HLA) antibodies that can elicit adverse effects on kidney transplantation (KT) outcomes. We investigated the correlation between levels of AT1R-Ab and ETAR-Ab and postoperative outcomes in KT recipients. METHODS: Pre-KT and post-KT serum from 79 patients was collected. Post-KT serum was collected within 1 year after KT or simultaneously as the biopsy. Levels of AT1R-Ab and ETAR-Ab were measured using enzyme-linked immunosorbent assay kits. AT1R-Ab >17.0 U/mL and ETAR-Ab >10.0 U/mL was considered to denote positivity according to manufacturer recommendations. We measured donor-specific antibodies against human leukocyte antigens (HLA-DSA) levels using LABScreen™ single-antigen kits. RESULTS: Seventy-nine (54 men, 25 women) formed the study cohort. Seven (8.7%) patients were positive for AT1R-Ab, 25 (31.6%) patients were positive for both AT1R-Ab and ETAR-Ab, and 47 (59.5%) were negative for both antibodies at all time points. No patients died during the study period. Patients with both AT1R-Ab and ETAR-Ab were associated with a higher prevalence of antibody-mediated rejection (AMR) and lower estimated glomerular filtration rate, but not allograft loss or delayed graft function. AT1R-Ab were associated with T-cell-mediated rejection, but the association was not significant. HLA-DSA were associated significantly with a higher creatinine level in serum at 12 months and 24 months in patients with AT1R-Ab and/or ETAR-Ab. CONCLUSIONS: AT1R-Ab, ETAR-Ab, and HLA-DSA were associated with a higher prevalence of AMR and decline in graft function. Measurement of levels of AT1R-Ab and ETAR-Ab in KT patients may be useful for stratification of immunological risk and identification of patients at a high risk of adverse graft outcome.

Clinical relevance of donor-specific human leukocyte antigen antibodies after pediatric liver transplantation.

Donor-specific human leukocyte antigen (HLA) antibodies (DSAs) have a significant role in graft survival after pediatric liver transplantation. To understand the significance of DSAs, a retrospective cohort study of 48 pediatric liver transplant recipients with posttransplant serum samples that were analyzed for DSAs was performed. According to their test results, the recipients were divided into a DSA-positive group and a DSA-negative group. Postoperative liver transplantation biopsies were performed in patients with abnormal liver function. The liver condition and prognosis of the recipients were recorded, and their association was analyzed. A total of 48 recipients were followed up for 2.7±0.8 years. DSA positivity was detected in 10 cases (20.8%). One case was positive for HLA class I and HLA class II antibodies, whereas 9 cases were positive for HLA class II antibodies, and the gene loci were HLA-DR and/or DQ. Antibody-mediated rejection (AMR) occurred in four of 10 patients in the DSA-positive group. Liver function was abnormal in 3 of 38 cases in the DSA-negative group. Multivariate analysis revealed that DSA positivity was an independent risk factor for liver insufficiency and long-term survival of recipients. In addition, Kaplan-Meier survival analysis demonstrated that there were significant differences in the survival of graft recipients between the DSA-positive group and the DSA-negative group (P<0.05). The positivity of DSAs after pediatric liver transplantation was closely related to the occurrence of AMR. These results suggested that DSAs should be routinely monitored post-operatively, and that DSA-positive recipients should be screened as soon as possible and given appropriate treatment.

De novo donor-specific HLA antibodies reduce graft survival rates and increase the risk of kidney transplant rejection: A single-center retrospective study.

BACKGROUND: We investigated the impact of de novo donor-specific anti-human leukocyte antigen antibodies (dnDSAs) on long-term death-censored graft survival and renal allograft rejection in kidney transplant recipients. METHODS: The sample for this retrospective cohort study comprised 121 recipients of kidney transplants with negative complement-dependent cytotoxicity crossmatches to their deceased donors. Recipients were divided into two groups: dnDSAs+ (n = 31) and dnDSAs- (n = 90). We evaluated rejection and long-term graft survival rates in the recipients along with pathologic changes in the transplanted kidneys. RESULTS: DnDSAs were identified in 31/121 patients (25.6%). The graft survival rate in the dnDSAs+ group was 87.1% (27/31) and that of the dnDSAs- group was 97.8% (88/90). The dnDSAs+ group had lower graft survival rates than patients without dnDSAs (p = 0.007). There was no difference in the graft survival rates between patients with high DSA mean fluorescence intensity (≥4000) and those with low intensity (<4000) (p = 0.669). There was also no difference in the graft survival rates of patients with HLA class I, II, and I + II dnDSAs (p = 0.571). The presence of dnDSA in serum was associated with a higher incidence of antibody- and T-cell-mediated rejection (p < 0.0001). Banff scores for arterial fibrointimal and arteriolar hyalin, thickening as well as C4d deposition differed for the dnDSAs+ and dnDSAs- groups (p < 0.05). CONCLUSION: DnDSAs were found to be associated with decreased long-term graft survival rates and increased rejection rates, often accompanied by C4d deposition.

Prenatal, perinatal, and postnatal factors associated with autism spectrum disorder cases in Xuzhou, China.

BACKGROUND: The aim of the present study was to explore the prenatal, perinatal, and postnatal risk factors in children with autism spectrum disorder (ASD) from Xuzhou, China by comparing them with healthy children. METHODS: Children with ASD who received rehabilitation training at special education schools and rehabilitation institutions in Xuzhou were selected as the ASD group, and healthy children during the same period were selected as the healthy non-ASD group. A questionnaire based on the possible causes and susceptibility factors of ASD in children was issued and given to all children in this study. RESULTS: The findings of the present study revealed a higher prevalence of prenatal, perinatal, and postnatal factors in children with ASD compared with healthy children. There were significantly more males than females in the ASD group, and the proportion of boys to girls was 5.81:1 (P<0.05). Logistic regression analysis suggested that the risk factors of male children developing ASD were feeding difficulties, poor living environment during pregnancy, maternal exposure to cigarette smoking during pregnancy, and perinatal hypoxia. Factors associated with ASD risk among were identified, such as living environment during pregnancy, delivery method, feeding difficulties, and epilepsy (P<0.05). Feeding difficulties and living in the countryside during pregnancy might be risk factors for ASD in girls according to the logistic regression analysis. CONCLUSIONS: This survey confirmed the high prevalence of prenatal, perinatal, and postnatal factors in children with ASD. Some of these factors may be effective entry points for the prevention and treatment of ASD.

Interpretation of the HLA epitopes-Continuous dilution method for detection of high-titer IgG HLA antibody.

BACKGROUND: The presence or absence of human leukocyte antigen (HLA) antibodies, especially the strength of donor-specific HLA antibodies (DSAs), has important roles in clinical evaluation and diagnostic decision-making for solid-organ transplantation. Dilution patterns help to give a new sight of HLA epitopes. "Epitope matching" is likely to lower the risk of developing DSA and increase the likelihood of matching a compatible donor. METHODS: We collected data evaluating HLA antibodies with a titration study using mean fluorescence intensity. RESULTS: Diluting the serum of recipients can reduce potential inhibitory effects, accurately evaluate the intensity of donor-specific HLA antibodies, and guide surgeons to take or not take intervention measures. Dilution patterns also help to give a new sight of HLA epitopes. CONCLUSION: We believe that from the viewpoint of HLA antibodies, the dilution model can provide new tools and insights for the study of HLA epitopes.

Bacterial endotoxin decreased histone H3 acetylation of bovine mammary epithelial cells and the adverse effect was suppressed by sodium butyrate.

BACKGROUND: In practical production, dairy cows are frequently exposed to bacterial endotoxin (lipopolysaccharide, LPS) when they are subjected to high-concentrate diets, poor hygienic environments, as well as mastitis and metritis. Histone acetylation is an important epigenetic control of DNA transcription and a higher histone acetylation is associated with facilitated transcription. LPS might reduce histone acetylation in the mammary epithelial cells, resulting in lower transcription and mRNA expression of lactation-related genes. This study was conducted to investigate the effect of LPS on histone acetylation in bovine mammary epithelial cells and the efficacy of sodium butyrate (SB) in suppressing the endotoxin-induced adverse effect. Firstly, the bovine mammary epithelial cell line MAC-T cells were treated for 48 h with LPS at different doses of 0, 1, 10, 100, and 1000 endotoxin units (EU)/mL (1 EU = 0.1 ng), and the acetylation levels of histones H3 and H4 as well as the histone deacetylase (HDAC) activity were measured. Secondly, the MAC-T cells were treated for 48 h as follows: control, LPS (100 EU/mL), and LPS (100 EU/mL) plus SB (10 mmol/L), and the acetylation levels of histones H3 and H4 as well as milk gene mRNA expressions were determined. RESULTS: The results showed that HDAC activity increased linearly with increasing LPS doses (P < 0.01). The histone H3 acetylation levels were significantly reduced by LPS, while the histone H4 acetylation levels were not affected by LPS (P > 0.05). Sodium butyrate, an inhibitor of HDAC, effectively suppressed the endotoxin-induced decline of histone H3 acetylation (P < 0.05). As a result, SB significantly enhanced the mRNA expression of lactation-related genes (P < 0.05). CONCLUSIONS: The results suggest one of the adverse effects of LPS on the lactation of bovine mammary gland epithelial cells was due to decreasing histone H3 acetylation through increasing HDAC activity, whereas the endotoxin-induced adverse effects were effectively suppressed by SB.

Scenario analysis of ETS revenue allocation mechanism of China: based on a dynamic CGE model.

The successful establishment of China's emission trading scheme (ETS) could lead the next generation of global climate carbon markets in industrializing and developing countries. The allocation of ETS revenue from auctioning carbon emission allowance is important for the achievement of China's joint targets of economic growth, mitigation, and welfare improvement. This study develops a dynamic CGE model to evaluate the effects of different ETS revenue allocation mechanisms and identifies the proper mechanism for China's ETS design. Ten scenarios including business as usual (BAU), no ETS revenue allocation incentive (NA) and other eight ETS revenue allocation scenarios are designed. Simulation results indicate that the tradeoff between economic cost and environmental benefit exists under different ETS revenue allocation mechanisms. ETS revenue is suggested to allocate to household sector through reducing indirect tax and, after 2020, a certain proportion of ETS revenue could be allocated to production sector for improving energy-saving technology (i.e., STP mechanism). This study provides references for policymakers in China to design effective and realistic ETS-related policies. A similar study could be conducted to explore the proper ETS and the revenue allocation policies in other countries that have similar national conditions to China, such as other BRICS countries.

Bacterial Lipopolysaccharide Induced Alterations of Genome-Wide DNA Methylation and Promoter Methylation of Lactation-Related Genes in Bovine Mammary Epithelial Cells.

Bacterial lipopolysaccharide (LPS) could result in poor lactation performance in dairy cows. High methylation of DNA is associated with gene repression. However, it is unclear whether LPS could suppress the expression of lactation-related genes by inducing DNA methylation. Therefore, the objective of this study was to investigate the impact of LPS on genome-wide DNA methylation, using methylated DNA immunoprecipitation with high-throughput sequencing (MeDIP-seq) and on the promoter methylation of lactation-related genes using MassArray analysis in bovine mammary epithelial cells. The bovine mammary epithelial cell line MAC-T cells were treated for 48 h with LPS at different doses of 0, 1, 10, 100, and 1000 endotoxin units (EU)/mL (1 EU = 0.1 ng). The results showed that the genomic methylation levels and the number of methylated genes in the genome as well as the promoter methylation levels of milk genes increased when the LPS dose was raised from 0 to 10 EU/mL, but decreased after further increasing the LPS dose. The milk gene mRNA expression levels of the 10 EU/mL LPS treatment were significantly lower than these of untreated cells. The results also showed that the number of hypermethylated genes was greater than that of hypomethylated genes in lipid and amino acid metabolic pathways following 1 and 10 EU/mL LPS treatments as compared with control. By contrast, in the immune response pathway the number of hypomethylated genes increased with increasing LPS doses. The results indicate LPS at lower doses induced hypermethylation of the genome and promoters of lactation-related genes, affecting milk gene mRNA expression. However, LPS at higher doses induced hypomethylation of genes involved in the immune response pathway probably in favor of immune responses.

Comparison of affective and semantic priming in different SOA.

Researchers have been at odds on whether affective or semantic priming is faster or stronger. The present study selects a series of facial expression photos and words, which have definite emotional meaning or gender meaning, to set up experiment including both affective and semantic priming. The intensity of emotion and gender information in the prime as well as the strength of emotional or semantic (in gender) relationship between the prime and the target is matched. Three groups of participants are employed separately in our experiment varied with stimulus onset asynchrony (SOA) as 50, 250 or 500 ms. The results show that the difference between two types of priming effect is revealed when the SOA is at 50 ms, in which the affective priming effect is presented when the prime has negative emotion. It indicates that SOA can affect the comparison between the affective and semantic priming, and the former takes the priority in the automatic processing level.

Neuroprotective mechanism of modafinil on Parkinson disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

AIM: To observe the neuroprotective mechanism of modafinil on Parkinson disease (PD) models induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). METHODS: The model of PD was induced by intraperitoneally injecting MPTP into C57BL/6J mice for 4 d. Modafinil (i.p., 50 or 100 mg/kg(-1)/d(-1)) was administered at 30 min following MPTP for 4 d and for another 10 d continuously. The contents of dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5-HT), gamma-aminobutyric acid (GABA), glutamine (Glu) in the striatum, and the contents of GABA, Glu, malondialdehyde (MDA), and glutathione (GSH) in the substantia nigra (SN) of model mice were determined. RESULTS: Modafinil (50 and 100 mg/kg) prevented against the decrease of the contents of DA, 5-HT, and NA in the striatum and GSH, GABA in the SN induced by MPTP, but reduced the increase of MDA in the SN and GABA in the striatum induced by MPTP. Modafinil preferentially inhibited striatal GABA release, but it did not change the increase of nigrostriatal Glu release induced by MPTP. CONCLUSION: The anti-oxidation and the modulation of nigrostriatal GABA and striatal NA and 5-HT release contributed to the neuroprotective effects of modafinil on PD induced by MPTP.