Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Objective:To investigate the associations of onset age, diabetes duration, and glycated hemoglobin (HbA1c) levels with ischemic stroke risk in type 2 diabetes patients.Methods:The participants were from Comprehensive Research on the Prevention and Control of the Diabetes in Jiangsu Province. The study used data from baseline survey from December 2013 to January 2014 and follow-up until December 31, 2021. After excluding the participants who had been diagnosed with stroke at baseline survey and those with incomplete information on onset age, diabetes duration, and HbA1c level, a total of 17 576 type 2 diabetes patients were included. Cox proportional hazard model was used to calculate the hazard ratio ( HR) and 95% CI of onset age, diabetes duration, and HbA1c level for ischemic stroke. Results:During the median follow-up time of 8.02 years, 2 622 ischemic stroke cases were registered. Multivariate Cox proportional risk regression model showed that a 5-year increase in type 2 diabetes onset age was significantly associated with a 5% decreased risk for ischemic stroke ( HR=0.95, 95% CI: 0.92-0.99). A 5-year increase in diabetes duration was associated with a 5% increased risk for ischemic stroke ( HR=1.05, 95% CI: 1.02-1.10). Higher HbA1c (per 1 standard deviation increase: HR=1.17, 95% CI: 1.13-1.21) was associated with an increased risk for ischemic stroke. Conclusion:The earlier onset age of diabetes, longer diabetes duration, and high levels of HbA1c are associated with an increased risk for ischemic stroke in type 2 diabetes patients.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an underdiagnosed genetic heart disease worldwide. The management and prognosis of obstructive HCM (HOCM) and non-obstructive HCM (HNCM) are quite different, but it also remains challenging to discriminate these two subtypes. HCM is characterized by dysmetabolism, and myocardial amino acid (AA) metabolism is robustly changed. The present study aimed to delineate plasma AA and derivatives profiles, and identify potential biomarkers for HCM. METHODS: Plasma samples from 166 participants, including 57 cases of HOCM, 52 cases of HNCM, and 57 normal controls (NCs), who first visited the International Cooperation Center for HCM, Xijing Hospital between December 2019 and September 2020, were collected and analyzed by high-performance liquid chromatography-mass spectrometry based on targeted AA metabolomics. Three separate classification algorithms, including random forest, support vector machine, and logistic regression, were applied for the identification of specific AA and derivatives compositions for HCM and the development of screening models to discriminate HCM from NC as well as HOCM from HNCM. RESULTS: The univariate analysis showed that the serine, glycine, proline, citrulline, glutamine, cystine, creatinine, cysteine, choline, and aminoadipic acid levels in the HCM group were significantly different from those in the NC group. Four AAs and derivatives (Panel A; proline, glycine, cysteine, and choline) were screened out by multiple feature selection algorithms for discriminating HCM patients from NCs. The receiver operating characteristic (ROC) analysis in Panel A yielded an area under the ROC curve (AUC) of 0.83 (0.75-0.91) in the training set and 0.79 (0.65-0.94) in the validation set. Moreover, among 10 AAs and derivatives (arginine, phenylalanine, tyrosine, proline, alanine, asparagine, creatine, tryptophan, ornithine, and choline) with statistical significance between HOCM and HNCM, 3 AAs (Panel B; arginine, proline, and ornithine) were selected to differentiate the two subgroups. The AUC values in the training and validation sets for Panel B were 0.83 (0.74-0.93) and 0.82 (0.66-0.98), respectively. CONCLUSIONS The plasma AA and derivatives profiles were distinct between the HCM and NC groups. Based on the differential profiles, the two established screening models have potential value in assisting HCM screening and identifying whether it is obstructive.
Humans ; Amino Acids ; Cysteine ; Cardiomyopathy, Hypertrophic/diagnosis* ; Biomarkers ; Proline ; Arginine ; Ornithine ; Glycine ; Choline

Objective:To retrieve relevant evidence on exercise assessment and exercise training for children with congenital heart disease at home and abroad, and to summarize the best evidence to provide reference for clinical medical staff.Methods:UpToDate, National Guidelines Clearinghouse (NGC), Registered Nurses Association of Ontario (RNAO), Scottish Intercollegiate Guidelines Network (SIGN), National Institute for Health and Care Excellence (NICE), BMJ Best Practice, American Heart Association (AHA), Cochrane Library, Joanna Briggs Institute(JBI) Evidence-Based Health Care Center Database, PubMed, CINAHL, China Biomedical Literature Database, Yimaitong, Wangfang Database, CNKI were searched, related evidence on exercise assessment and exercise training for children with congenital heart disease. The search period was from the establishment of the database to March 2021. Clinical decision-making and recommended practice used retrospective evaluation methods for quality evaluation; guidelines used the 2012 version of the clinical guideline research and evaluation system (AGREE Ⅱ) for evaluation; systematic reviews used the systematic evaluation tool (AMSTAR) for evaluation; expert consensus used JBI (2016 version) evaluate the authenticity evaluation tools of opinions and consensus articles. Two researchers independently evaluated the literature, combined with the judgment of professionals, and extracted the literature data that met the standards.Results:A total of 15 documents were included, including 2 clinical decisions, 4 guidelines, 1 recommended practice, 5 systematic reviews, 3 expert consensus, and 22 best evidences. Including related personnel, exercise evaluation, exercise monitoring, exercise classification, exercise training, and exercise follow-up.Conclusions:This study summarizes the best evidence of exercise assessment and exercise training for children with congenital heart disease, and provides evidence-based evidence for clinical practice. It is recommended that children with congenital heart disease undergo exercise assessment and formulate a personalized exercise training program to promote the transformation of the best evidence into clinical practice.

【Objective】 To investigate the effect of HLA-G expressed in platelets on Tax protein of human T cell leukemia type 1 virus (HTLV-1). 【Methods】 Platelets were isolated from anticoagulant whole blood, and HLA-G molecule on platelet membrane was detected by flow cytometry. The content of secretory HLA-G before and after platelet lysis was detected by ELISA, HTLV-1 human lymphoma cells MT2 were cultured with platelet lysate (PL). The effect of HLA-G in platelets on the expression of HTLV-1 protein Tax was evaluated by Western blot (WB). 【Results】 Membrane type mHLA-G was highly expressed on the surface of platelet membrane. The expression of secretory sHLA-G (ng/mL) increased after platelet lysis (15.73±1.01) vs (6.65±0.47), the expression of sHLA-G increased with the increase of platelet concentration in a dose-dependent manner. Compared with fetal bovine serum, PL significantly promoted the high expression of HLA-G protein and HTLV-1 virus tax protein in MT2 cells, and the addition of anti-HLA-G antibody to PL could effectively inhibit the expression of Tax and HLA-G protein. 【Conclusion】 High expression of immune tolerance molecule HLA-G on platelets can induce high expression of HTLV-1 protein Tax in human lymphoma cell MT2, which contributes to viral infection.