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Autoimmune diseases such as ankylosing spondylitis (AS) can be driven by emerging neoantigens that disrupt immune tolerance. Here, we developed a workflow to profile posttranslational modifications involved in neoantigen formation. Using mass spectrometry, we identified a panel of cysteine residues differentially modified by carboxyethylation that required 3-hydroxypropionic acid to generate neoantigens in patients with AS. The lysosomal degradation of integrin αIIb [ITGA2B (CD41)] carboxyethylated at Cys96 (ITGA2B-ceC96) generated carboxyethylated peptides that were presented by HLA-DRB1*04 to stimulate CD4 + T cell responses and induce autoantibody production. Immunization of HLA-DR4 transgenic mice with the ITGA2B-ceC96 peptide promoted colitis and vertebral bone erosion. Thus, metabolite-induced cysteine carboxyethylation can give rise to pathogenic neoantigens that lead to autoreactive CD4 + T cell responses and autoantibody production in autoimmune diseases.

Glioblastoma (GBM) is a lethal cancer with limited therapeutic options. Dendritic cell (DC)-based cancer vaccines represent a promising approach for GBM treatment. Clinical studies suggest that other immunotherapeutic agents including anti-PD-1 and immune adjuvant poly I:C may be combined with DC vaccines to further enhance antitumor activity. Here we report a GBM case with combination immunotherapy consisting of DC vaccines, anti-PD-1 and poly I:C as well as a chemotherapeutic agent cyclophosphamide that were integrated with the standard chemoradiation therapy for > 5 years. The patient who received DC vaccines loaded with multiple forms of tumor antigens including mRNA-tumor associated antigens (TAAs), mRNA-neoantigens, and hypochlorous acid-oxidized tumor lysates. Furthermore, mRNA-TAAs were modified with a novel TriVac technology which fuses TAAs with a destabilization domain and inserts TAAs into a full-length LAMP-1 to enhance MHC class I and II antigen presentation, respectively. The treatment consisted of 42 DC cancer vaccine infusions, 26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions. The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells. No immunotherapy related adverse events were observed during the treatment. Robust anti-tumor CD4+ and CD8+ T cell responses were detected. The patient remains free of disease progression as of July, 2022. Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment. A large scale trial to validate these findings is warranted. Protocol numbers: 201708152377, 20202014-F-1

Chitosan oligosaccharide (COS), a natural polysaccharide with good antioxidant and anti-inflammatory properties, is the depolymerized product of chitosan possessing various biological activities. The present study was designed to investigate the possible anti-aging effect of COS on the aging model mouse induced by d-galactose (d-gal) and explore the underlying mechanism. In the experiment, 48 male Kunming mice (KM mice) were randomly divided into the normal group, model group, positive group, and low-medium-high dose polysaccharide groups (300, 600, 1200 mg/kg/day). The results showed that COS, by intragastric gavage after subcutaneous injection of d-gal (250 mg/kg/day) into the neck of mice consecutively for eight weeks, gradually recovered the body weight, the activity of daily living, and organ indices of mice, as well as effectively ameliorated the histological deterioration of the liver and kidney in mice triggered by d-gal. To be specific, COS obviously improved the activities of antioxidant enzymes in liver and kidney of KM mice, including catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD), as well as decreased malondialdehyde (MDA) levels when compared with those in model group mice. Furthermore, COS not only elevated the diminished levels of serum immunoglobulin G (IgG) and IgM induced by d-gal, but also significantly inhibited the d-gal-caused upregulation of serum alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), uric acid (UA) and creatinine (CREA) levels as compared with those of mice in the model group. These results demonstrate that COS has an obvious anti-aging activity in d-gal-induced subacute aging mice, the mechanism of which, to some extent, is associated with enhancing the antioxidant defenses, reducing oxidative stress, and improving the immune function of aging model mice.

Chronic kidney disease (CKD) stage 3 was divided into stage G3a and stage G3b in the 2013 Kidney Disease Improving Global Outcomes guidelines. Whether it is appropriate to regard 45 mL/min/per 1.73 m2 as the threshold value of G3a/G3b staging and whether dividing CKD stage 3 into G3a/G3b plays a useful role in assessing the prognosis of patients with IgA nephropathy (IgAN) remain unknown. Three hundred and ninety patients from the First Affiliated Hospital of Zhengzhou University and Peking University First Hospital diagnosed with IgAN in CKD stage 3 were enrolled and successfully followed up. Cox proportional hazards model was used to analyze hazard ratios of reaching the composite endpoints (doubling of serum creatinine, end-stage renal disease: estimated glomerular filtration rate (eGFR)

How to evaluate vocation education performance is one of the difficulties and hot research fields for the researchers related. The paper presents a new model for evaluating vocation education performance based on the principle of analytic hierarchy process and fuzzy comprehensive evaluation. First an evaluation indicator system of vocation education performance is designed through analyzing the characteristics of vocation learners behavior; Secondly in constructing the comprehensive evaluation model for vocation education performance, analytic hierarchy process and fuzzy comprehensive evaluation are combined and two level fuzzy evaluation is adopted to satisfy the dynamics, subjective and transitional characteristics of indicators and improve evaluation accuracy. Thirdly datum from three vocational colleges are taken for examples to verify the validity and feasibility of the model and the experimental results show that the model can evaluate vocation education performance practically and can help vocation education service providers take corresponding concrete measures to enhance its education performance.

To determine the expression of mTOR, Becline-1, LC3 and p62 in the peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) and assess their relationship with disease activity and immunologic features. The expression of mTOR, Becline-1, LC3 and p62 was detected by RT-PCR in 81 SLE subjects and 86 age- and sex-matched healthy controls. Data regarding demographics and clinical parameters were collected. Disease activity of SLE was evaluated according to the SLE Disease Activity Index (SLEDAI) score. Independent sample t-test was used to analyze the expression of mTOR, Becline-1, LC3, and p62 in the two groups. Pearson’s or Spearman’s correlation was performed to analyze their relationship with disease activity and immunologic features. The mean levels of Becline-1, LC3 and p62 mRNA were significantly higher in SLE patients than the controls (9.96×10-4 vs 7.38×10-4 for Becline-1 with P

We aimed to determine the prevalence of hypovitaminosis D in patients with autoimmune rheumatic diseases (ARDs) in China and its association with demographic characteristics of the patients. We recruited 384 patients in this cross-sectional study including 121 cases of systemic lupus erythematosus (SLE), 131 rheumatoid arthritis (RA), 102 spondyloarthritis (SpA) and 30 other ARDs. For each patient, demographic information was collected and serum concentration of 25OHD3 was measured by electrochemiluminescence immunoassay (ECLIA). The multivariate logistic regression model was used to investigate the association between vitamin D deficiency and patient characteristics. The mean serum vitamin D level of the 384 patients was 18.91 (8.12) ng/mL, and the median age was 37.33 (12.01) yrs. Among these patients, 222 (57.81%) and 127 (33.07%) were found to be vitamin D deficiency and insufficiency, respectively. From the disease perspective, the percentages of insufficiency and deficiency were as follow: 97.52% and 84.30% in SLE, 87.02% and 48.85% in RA, 88.24% and 40.20% in SpA, 90.89% and 57.81% in other ARDs patients. The causative factors for vitamin D deficiency included SLE per se (OR 12.54, P < 0.001) and high body mass index (BMI) (OR 1.88, P < 0.001). However, the seniors were less likely to have vitamin D deficiency (OR 0.95, P = 0.005). No correlation was disclosed between vitamin D deficiency and gender or disease duration. Hypovitaminosis D is highly prevalent among autoimmune rheumatic diseases population in China. The SLE per se and the obesity are the risk factors for vitamin D deficiency. Clinicians are advised to supplement vitamin D in these patients.

To investigate the effect and current situation of the standardized construction of laboratories of schis- tosomiasis control institutions in Hubei Province, so as to provide the evidence for establishing and improving the quality control system of diagnosis of schistosomiasis after the transmission of schistosomiasis was under control.According to the procedures of self-examination, field operation, and laboratory on-site, five laboratories were assessed, and all the results were analyzed comparatively.The average number of staffs were (7.00±1.58) persons, and the staffs of the laboratories of the schistosomiasis control institutions with senior professional titles in the city level were more than that in the county level (t = 5.563, P0.05). The average space was (3.20±1.64) rooms, and the average area was (117.00±88.29) m2. The average score of field operation was (96.40±4.49) points. The average score of laboratory on-site assessment was (106.6±6.15) points. The highest and lowest of the laboratory on-site assessment scores were environment and facilities (19.60 ± 0.55) points and management system of laboratory quality control (15.70±2.39) points (F = 2.869, P0.05), respectively.The cultivation of laboratory staff should be strengthened, and the diagnostic capacity should be maintained and improved. The laboratory quality control system should be paid more attention to, and the construction and management of schistosomiasis laboratories should be standardized.

To investigate the incidence and correlative factors of metabolic syndrome (MS) in patients with systemic lupus erythematosus (SLE).A total of 116 SLE patients and 115 controls were enrolled into the study. The incidence of MS, SLE disease activity index (SLEDAI) of patients with SLE combined with MS (MS-SLE) and patients without MS (n-MS-SLE), lupus characteristics, cumulative glucocorticoids, administration dose of glucocorticoids and hydroxychloroquine were compared between SLE group and the control group.The incidence of MS of SLE group was obviously higher than that of the control (34.48% vs 14.78%, P0.05). The ratios of patients with lower HDL-C, higher TG and higher blood pressure in SLE group (50.86%, 56.03%, 46.55%) were higher than those in the controls (34.78%, 16.52%, 20.00%, all P0.05). MS-SLE group had significantly higher mean waist circumference, BMI, systolic blood pressure and diastolic blood pressure and lower HDL-C than n-MS-SLE group (all P0.05). No significant difference was found regarding duration of disease, renal involvement, ESR, C-reactive protein,high-sensitivity C-reactive protein, SLEDAI, cumulative and current glucocorticoids use in MS-SLE group and n-MS-SLE group. The ratio of patients taking hydroxychloroquine in n-MS-SLE group was higher than that of MS-SLE group (46.05% vs 15.00%, P0.05).Patients with SLE has a higher incidence rate of MS. Hydroxychloroquine may reduce their MS incidence.

To study the effects of CD147 on neutrophil on matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) production by fibroblast-like synoviocytes (FLS) and the invasive potential of FLS in rheumatoid arthritis(RA).FLS were isolated from the synovial tissues which were resected from the patients with rheumatoid arthritis (RA) and ostarthritis (OA) during synovectomy, and CD14, CD90 on RA FLS were detected by FCM. HL-60 cells were differentiated into mature neutrophil by alltransretinoic acid (ATRA) and the degree of cell differentiation was detected through NBT reduction reaction. CD147 expression on the differentiated and undifferentiated HL-60 cells and FLS were detected by FCM. The release and activity of MMP-2 and MMP-9 were detected in the supernantents of HL-60 cells cocultured with RA FLS by Gelatin zymography. The invasive potential of RA FLS was detected by invasion assay. To further investigate the effect of CD147 on neutrophil on MMP production by FLS and the invasive potential of FLS in RA, antagonist peptide against EMMPRIN/CD147 (AP-9) was added to the coculture.The experimental system of FLS separation and culture and HL-60 differentiation were established successfully. The isolated FLS of RA were characterized by negative CD14 and positive CD90. CD147 expression on the differentiated HL-60 cells was higher than that on the undifferentiated HL-60 cells, and CD147 expression on both of them were higher than that on RA FLS (P0.05). The expressions of Pro-MMP-2, MMP-2 produced by RA FLS were higher than that produced by OA FLS (P0.05). Pro-MMP-2, MMP-2, Pro-MMP-9 and MMP-9 were significantly increased when RA FLS were cocultured with the undifferentiated or differentiated HL-60 cells (P0.05), and Pro-MMP-2 and MMP-2 in differentiated HL-60 cells cocultured with RA FLS increased more than those in the undifferentiated HL-60 cells cocultured with RA FLS (P0.05). The increase was inhibited by AP-9 significantly (P0.05). Invasion assay showed that the invasive potential of RA FLS was higher than that of OA FLS (P0.05), and the undifferentiated or differentiated HL-60 cells increased the invasive potential of RA FLS (P0.05), which could be blocked by AP-9.Neutrophil might increase the production of MMP-2 and MMP-9 and enhanced the invasion of RA FLS via CD147, which can be inhibited by HAb18G/CD147 antagonistic peptide (AP9). Our research on RA pathogenesis and the mechanism of cartilage destruction may give us some good ideas for RA therapy in future.

To investigate the modulation of rhC II 250-270 peptide on special humoral immune response in the course of oral administration.ELISA was used to determine antigen-specific antibodies in mice sera. The frequency of anti-C II and anti-C II (250-270) antibody-forming spleen cells was measured by ELISPOT.The level of C II- and C II (250-270)- specific IgG in serum from the mice fed with rhC II (250-270) were (0.82+/-0.02) and (0.84+/-0.04) respectively, and lower significantly than those of collagen-induced arthritis (CIA) control group. The anti-C II (250-270) antibody responses were suppressed obviously (P0.01). The frequency of antibody-forming cells in the spleen from rhC II (250-270)-fed mice were (158+/-9 counts/well) and (181+/-10 counts/well) respectively, and also were reduced significantly when compared with that in CIA control group (247+/-16 counts/well)(P0.05).Oral rhC II (250-270) could induce specific suppression of humoral responds in CIA. These findings together with a better understanding of the mechanisms of oral tolerance and regulation of humoral immune response in CIA, will help the development of innovative therapeutic intervention for rheumatoid arthritis.

To investigate the expression of CD147 both on cellular membrane and in culture supernatant of in vitro cultured THP-1 cells and monocytes of RA patients before and after stimulation with phorbol myristate acetate (PMA).Human peripheral blood monocytes (HPBMs) were segregated from RA patients by adherent culture method. After the HPBMs and THP-1 cells were stimulated with PMA, the expression rate and expression intensity of CD147 on THP-1 cells and HPBMs of RA patients were determined by flow cytometry. The soluble CD147 levels in culture supernatant of in vitro cultured THP-1 cells and HPBMs were quantified by double antibody Sandwich ELISA.The soluble CD147 in the supernatant of cultured THP-1 cells and HPBMs was detectable before PMA stimulation. Both cells showed high CD147 expression. After PMA stimulation, soluble CD147 level in the supernatant of THP-1 cells increased. CD147 expression on THP-1 cells firstly increased then decreased and kept stable for several days. CD147 expression on HPBMs of RA patients decreased, but CD147 level in the culture supernatant of HPBMs of RA patients increased and kept stable for 2 days.CD147 molecule can be shed from the membrane of THP-1 cells and HPBMs of RA patients, or it can be directly secreted into the culture supernatant from the two kinds of cells. PMA can up-regulate the level of soluble CD147.

To induce bone marrow mesenchymal stem cells or bone marrow stroma cells (MSCs) to differentiate directionally towards chondrocytes in vitro and then identify the differentiated cells.MSCs were isolated from bone marrows of healthy adult human donors and then the cultured. MSCs at the 3rd passage were induced by TGF-beta1, dexamethasone(Dex) and Vitamin C(Vit C). 14 days later, micro-cell aggregates formed by the induced MSCs were embedded in paraffin, sectioned and stained with HE, toluidine blue or anti-type II collagen mAb (Col II). The expression of Col II in the induced MSCs also were detected by Western blot and RT-PCR.The induced cells exhibited a chondrocyte-like morphology.The staining of toluidine blue and Col II on extracellular matrix in the micro-cell aggregates was positive. Western blot and RT-PCR showed that Col II was only expressed in the induced cells.MSCs can differentiate into chondrocytes under the induction of TGF-beta1, Dex and Vit C.

To investigate the prevalence and epidemiologic characteristics of seronegative spondyloarthritis (SpAs) in Chinese army force in different areas.4-phase survey was conducted in 21 750 Chinese army, including: face-to-face interviews with standardized COPCORD questionnaires (Phase I screening); further examination on the suspected cases; identification of inflammatory joint and spinal diseases (Phase II); identification of SpAs (AS and uSpA) by more than two experienced specialists in rheumatology; further examination with X-rays and laboratory detection of HLA-B27 (Phase III); and data analysis (Phase IV).Among 21 750 army men, 21 cases of RA, 106 cases of SpAs were identified, with prevalence rates of 0.966 per thousand, 4.87 per thousand respectively. In 106 cases of SpAs, there were 46 cases of ankylosing spondylitis (AS), 52 cases of undifferentiated SpAs (uSpAs) with the prevalence rates of 2.11 per thousand and 2.39 per thousand respectively. Few cases of reactive arthritis (ReA) and Reiter's syndrome (RS) were identified (6 and 1 cases respectively). The prevalence of AS, uSpAs were higher in navy than that in the ground force or the air force. Soldiers in cold and damp areas had higher prevalence rates than that in the plain and drought areas.The prevalence of SpA (especially AS and uSpA) in Chinese army force was similar to that in the civilians. SpA (AS and uSpA) was more prevalent seen in the Navy. The incidence of SpA (AS and uSpA) was influenced by environmental factors such as coldness and dampness.

The majority of research found that the positive rate of MOC-31 is higher in lung carcinoma than that in pleural mesothelioma. So MOC-31 is regarded as an important factor in differentiating diagnosis of lung carcinoma from pleural mesothelioma. But there are also few contrary reports. CD56 (neural cell adhesion molecule) is a sensitive factor in diagnosis of small cell lung carcinoma (SCLC), but the reports about its diagnostic sensitivity in non-small cell lung carcinoma (NSCLC) are different. This study was conducted to investigate the significance of MOC-31 and CD56 in diagnosis of human lung carcinoma.Immunohistochemical method (S-P) was used to detect MOC-31 and CD56 expression in 92 cases of lung carcinoma.The positive rate of MOC-31 in lung carcinoma was 98.9% (91/92), among which, 98.6% (72/73) in NSCLC, 100% (19/19) in SCLC; the positive expression rate of CD56 in lung carcinoma was 30.4% (28/92), among which, 12.3% (9/73) in NSCLC, 100% (19/19) in SCLC. MOC-31 and CD56 expressions in adjacent lung tissue and normal lung tissue were negative.MOC-31 is an antibody which is highly sensitive and peculiar to lung carcinoma, whereas CD56 only showed sensitive to SCLC. Therefore, combined determination of MOC-31 and CD56 is more useful than that of single item in diagnosing SCLC.

Necessary and sufficient conditions for a maximal ancestral graph (MAnG) to be Markov equivalent to another MAnG and to a DAG are provided respectively. Also a polynomial-time algorithm for converting a MAnG into its equivalent DAG is given for the first time.