OBJECTIVE: To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia (AML) cells. METHODS: A TCR-like or TCR mimic antibody that can specifically recognize HLA-A*0201:WT1_126-134 ( RMFPNAPYL) complex (hereafter referred to as HLA-A2:WT1) was synthesized to evaluate the function of antigen processing and presentation machinery (APM) in AML cells. AML cell line THP1 was incubated with increasing concentrations of IFN-γ, hypomethylating agents (HMA), immunomodulatory drugs (IMiD), proteasome inhibitors (PI) and γ-secretase inhibitors (GSI), followed by measuring of HLA-ABC, HLA-A2 and HLA-A2:WT1 levels by flow cytometry at consecutive time points. RESULTS: The TCR-like antibody we generated only binds to HLA-A*0201⁺WT1⁺ cells, indicating the specificity of the antibody. HLA-A2:WT1 level of THP-1 cells detected with the TCR-like antibody was increased significantly after co-incubation with IFN-γ, showing that the HLA-A2:WT1 TCR like antibody could evaluate the function of APM. Among the anti-tumor agents screened in this study, GSI (LY-411575) and HMA (decitabine and azacitidine) could significantly increase the HLA-A2:WT1 level. The IMiD lenalidomide and pomalidomide could aslo upregulate the expression of HLA-A2:WT1 complex under certain concentrations of the drugs and incubation time. As proteasome inhibitors, carfilzomib could significantly decreased the expression of HLA-A2:WT1, while bortezomib had no significant effect on HLA-A2:WT1 expression. CONCLUSION HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function. Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Antineoplastic Agents/pharmacology* ; Antigen Presentation/drug effects* ; HLA-A2 Antigen/immunology* ; Receptors, Antigen, T-Cell/immunology* ; Cell Line, Tumor ; Interferon-gamma

Objective: To examine the independent and combined effects of pre-pregnancy BMI and gestational diabetes (GDM) on early adiposity rebound (AR) timing in children. Methods: Based on the "Ma'anshan Birth Cohort Study", 2 896 eligible maternal and infant pairs were recruited. In the cohort, we collected pre-pregnancy height, weight, 24 to 28 weeks GDM diagnosis, follow-up at 42 days, three months, six months, nine months of age, and every six months after one year of age, and continuously followed up to 6 years old, and obtained the child's length/height, weight, and other data. The intensity of the association between pre-pregnancy BMI, GDM, and early AR timing was analyzed by the multivariate logistic regression model. Multiplication and additive models were used to analyze how pre-pregnancy BMI and GDM influenced early AR timing in children. Results: The prevalence of underweight, average weight, overweight, and obesity before pregnancy were 23.2% (672), 66.4% (1 923), 8.7% (251), and 1.7% (50). The prevalence of GDM was 12.4%. We found that 39.3% of children had AR, and the average age at AR was (4.38±1.08). The results of multifactorial logistic regression analysis showed that pre-pregnancy overweight (OR=1.67,95%CI:1.27-2.19), pre-pregnancy obesity (OR=3.05,95%CI:1.66-5.56), and maternal GDM (OR=1.40,95%CI:1.11-1.76) were risk factors for early AR timing in children. In contrast, pre-pregnancy underweight (OR=0.60,95%CI:0.49-0.73) was a protective factor for early AR timing in children. Compared with the different effects of pre-pregnancy overweight/obesity and maternal GDM alone, the combined effect caused a higher risk of early AR timing in children, with OR values (95%CI) were 2.03 (1.20-3.44), 3.43 (1.06-11.12), respectively. The multiplication and additive models showed no interaction between pre-pregnancy BMI and GDM-influenced early AR timing in children. Conclusion: Higher pre-pregnancy BMI and maternal GDM are the independent risk factors for the early AR timing in children, and the co-occurrence of the two is higher risks, but there was no statistical interaction.
Child ; Infant ; Female ; Pregnancy ; Humans ; Adiposity ; Diabetes, Gestational/epidemiology* ; Overweight/epidemiology* ; Thinness ; Cohort Studies ; Body Mass Index ; Obesity

Objective::To observe the clinical efficacy of modified Simiaosan on synovitis of knee joint with damp-heat obstruction collateral syndrome and the effect on inflammatory factors and neuropeptide substances in synovial fluid. Method::One hundred and thirty-five patients were randomly divided into control group(67 cases) and observation group(68 cases) by random number table. Patients' intra-articular effusion was drawn out. Triamcinolone acetonide was injected into arthrosis for 2 times, 1 time/week, and aceclofenac sustained-release tablets were given for 4 weeks, 0.2 g/time, 1 time/day. In addition to the therapy of control group, patients in observation group were also given modified Simiaosan for 4 weeks, 1 dose/day. Before and after treatment, pain, swelling of knee joint and were scored, Western Ontario and McMaster University (WOMAC) were adopted for scoring knee score, and damp-heat obstruction syndrome and local signs of knee joint were also assessed. And levels of interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), hypersensitive C-reactive protein (hs-CRP), substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) were detected. Result::After treatment, scores of pain and swelling of knee joint in observation group were lower than those in control group (P<0.01). Scores of WOMAC, the total score, integral of damp-heat obstruction collateral syndrome, knee flexion-extension range score and floating patella test were all lower than those in control group (P<0.01). And levels of IL-1β, IL-6, TNF-α, hs-CRP, SP, CGRP, NPY and VIP were all lower than those in control group (P<0.01). Analyzed by rank sum test, the clinical efficacy in observation group was better than those in control group (Z=2.089, P<0.05). Conclusion::Modified Simiaosan can significantly alleviate pain and swelling symptoms, promote the recovery of knee joint function, and inhibit the expressions of proinflammatory factors and neuropeptides in synovial fluid, with a better clinical efficacy.