The purpose of the research is to provide a new standard for matching of HLA three-dimensional structure, and summarize the major permissible mismatch and immunogenic mismatch antigens. The molecular modeling method was used to create HLA molecular structures by Swiss Model Server, and the comparison of the differences among the alleles was done by SPDV software with the function of iterative magic fit. The results were recorded by relative mean square deviation (RMSD, nm). The differences among alleles were scattered below 0.06 nm for HLA-A and -B molecules, and below 0.03 nm for HLA-DRB1 molecules. On the basis of the statistical analysis, when RMSD is greater than 0.04 nm for -A and -B molecules and 0.02 nm for -DRB1 molecules, the difference is meaningful and can be related with graft versus host disease. When RMSD is lower than 0.02 nm for -A and -B molecules and 0.01 nm for -DRB1 molecules, the difference is decided unmeaningful. From the data, the permissible mismatch and immunogenic mismatch alleles within HLA-A, HLA-B and HLA-DRB1 molecules were summarized. Three-dimensional structure matching is a new area in the transplantation field, much research should be done in the future.

OBJECTIVETo determine the relationship between polymorphisms in the genes encoding IL-1, IL-6, and IL-10 with primary biliary cirrhosis (PBC) in Chinese population.

METHODSWhole-blood samples were taken from 77 patients with PBC and 160 healthy controls. DNA was extracted and the polymorphisms at positions IL-1 +3953, IL-1RN intron 2, IL-6 -174, and IL-10 -1082, -819, and -592 were determined by using sequence-specific polymerase chain reaction (SSP) or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

RESULTSThe frequency of IL-1RN1,1 allele in PBC group was significantly higher than in control group (90.9% vs 79.4%, P=0.026), and the frequency of IL-1RN1,2 in PBC group was significantly lower than in control group (6.5% vs 18.8%, P=0.013). There was no significant difference in the frequence of IL-1RN*2 allele between PBC group and control group (P=0.06). Of the 77 patients with PBC, 4 patients were IL-6 -174GC, 73 were IL-6 174GG. All the 160 health controls are IL-6 -174GG (P=0.0036). The frequence of IL-6 -174C allele in PBC group was significantly higher than that in control group (P=0.0038). No significant differences of polymorphisms for IL-1 +3953 and IL-10 (-1082, -819 and -592) were found between PBC group and control group.

CONCLUSIONThe polymorphisms of IL-1RN and IL-6 -174G/C appear to be associated with PBC, and the polymorphisms of IL-1 +3953 and IL-10 promoter gene are not associated with PBC in a Chinese population.

Adult ; Aged ; Female ; Humans ; Interleukin-1 ; genetics ; Interleukin-10 ; genetics ; Interleukin-6 ; genetics ; Liver Cirrhosis, Biliary ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; methods ; Polymorphism, Restriction Fragment Length

OBJECTIVETo investigate the association between Chinese patients with autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and the polymorphisms of cytotoxic T lymphocyte -associated antigen-4 (CTLA-4) gene promoter (-318) and exon 1 (+49).

METHODSThe CTLA-4 promoter (-318 T/C) and exon 1 (+49A/G) polymorphisms were genotyped via restriction fragment length polymorphism methods in 62 Chinese AIH patients, 77 Chinese PBC patients and 160 healthy controls.

RESULTSThere was no difference in the distribution of CTLA-4 promoter -318 T/C polymorphisms between AIH patients and controls, but the C allele frequency was significantly increased in patients with AIH, compared to controls (P=0.02, OR=2.43). The distribution of CTLA-4 gene exon 1 49 A/G genotypes exhibited significant difference between PBC patients and controls (P=0.006), and the frequency of G allele showed a significant increase in PBC group as compared with controls (P=0.0046, OR=1.8). Although the genotype distribution of the CTLA-4 exon 1-promoter gene displayed no significant difference between AIH and PBC patients and controls, the occurrence of GG-CC was increased in the patients of the two groups (AIH: 32.3%, PBC: 37.7%; control: 22.5%).

CONCLUSIONThe above findings suggest that the polymorphisms of CTLA-4 gene probably confer susceptibility to AIH and PBC in the Chinese population.

Adolescent ; Adult ; Aged ; Antigens, CD ; genetics ; Asian Continental Ancestry Group ; genetics ; CTLA-4 Antigen ; China ; Exons ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Hepatitis, Autoimmune ; ethnology ; genetics ; Humans ; Liver Cirrhosis, Biliary ; ethnology ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Promoter Regions, Genetic ; genetics

In intensity-modulated radiation therapy (IMRT), it is time-consuming to repeatedly adjust the objectives manually to obtain the best tradeoff between the prescribed dose of the planning target volume and sparing the organs-at-risk. Here we propose a new method to realize automatic multi-objective IMRT optimization, which quantifies the clinical preferences into the constraint priority list and adjusts the dose constraints based on the list to obtain the optimal solutions under the dose constraints. This method contains automatic adjustment mechanism of the dose constraint and automatic voxel weighting factor-based FMO model. Every time the dose constraint is adjusted, the voxel weighting factor-based FMO model is launched to find a global optimal solution that satisfied the current constraints. We tested the feasibility and effectiveness of this method in 6 cases of cervical cancer with IMRT by comparing the original plan and the automatic optimization plan generated by this method. The results showed that with the same PTV coverage and uniformity, the automatic optimization plan had a better a dose sparing of the organs-at-risk and a better plan quality than the original plan, and resulted in obvious reductions of the average V45 of the rectum from (41.99∓13.31)% to (32.55∓22.27)% and of the bladder from (44.37∓4.08)% to (28.99∓15.25)%.

OBJECTIVETo establish the association between the geometric anatomical characteristics of the patients and the corresponding three-dimensional (3D) dose distribution of radiotherapy plan via feed-forward back-propagation neural network for clinical prediction of the plan dosimetric features.

METHODSA total of 25 fixed 13-field clinical prostate cancer intensity-modulated radiation therapy (IMRT)/stereotactic body radiation therapy (SBRT) plans were collected with a prescribed dose of 50 Gy. With the distance from each voxel to the planned target volume (PTV) boundary, the distance from each voxel to each organ-at-risk (OAR), and the volume of PTV as the geometric anatomical characteristics of the patients, the voxel deposition dose was used as the plan dosimetric feature. A neural network was used to construct the correlation model between the selected input features and output dose distribution, and the model was trained with 20 randomly selected cases and verified in 5 cases.

RESULTSThe constructed model showed a small model training error, small dose differences among the verification samples, and produced accurate prediction results. In the model training, the point-to-point mean dose difference (hereinafter dose difference) of the 3D dose distribution was no greater than 0.0919∓3.6726 Gy, and the average of the relative volume values corresponding to the fixed dose sequence in the DVH (hereinafter DVH difference) did not exceed 1.7%. The dose differences among the 5 samples for validation was 0.1634∓10.5246 Gy with percent dose differences within 2.5% and DVH differences within 3%. The 3D dose distribution showed that the dose difference was small with reasonable predicted dose distribution. This model showed better performances for dose distribution prediction for bladder and rectum than for the femoral heads.

CONCLUSIONWe established the relationships between the geometric anatomical characteristics of the patients and the corresponding planning 3D dose distribution via feed-forward back-propagation neural network in patients receiving IMRT/SBRT for the same tumor site. The proposed model provides individualized quality standards for automatic plan quality control.