Effects of a home-based exercise combined yoga and resistance training in enthesitis-related arthritis in China: study protocol for a randomised controlled trial.

INTRODUCTION: Enthesitis-related arthritis (ERA) is a category of juvenile idiopathic arthritis (JIA). The complications of JIA include pain, muscle weakness, limited movement and worsening quality of life. Yoga is an effective exercise therapy for rheumatoid arthritis and may have similar benefits for JIA. Considering the limitation of yoga for strengthening muscles, combined yoga and resistance training (CYRT) may compensate for the shortcomings and provide more benefits for JIA patients. Despite this, there is currently a lack of studies investigating the effectiveness of CYRT for JIA patients. Due to the inaccessibility of traditional exercise therapy, home-based exercise is needed. The study aims to assess the effectiveness of home-based CYRT on JIA. METHODS AND ANALYSIS: This is a 12-week randomised single-blind controlled trial study. 60 patients with ERA will be randomised into two groups: the home-based exercise group (HBE) and the health education (HE) group. The HBE group (n=30) will perform the CYRT programme 3 times a week at home for 12 weeks and receive HE. The HE group (n=30) will only receive HE. The outcomes include primary outcome (pain levels) and secondary outcomes (lower limb muscle strength, motion range of joint, aerobic fitness, function ability, fatigue levels, mental health, quality of life and blood biomarkers). The assessments will be conducted at baseline, postintervention (12 weeks) and follow-up (24 weeks). Data will be analysed by intention to treat. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine in December 2023 (approval no. XHEC-C-2023-059-3). This study will require informed consent from all subjects and guardians of children under 18 years of age. The findings will be published in a peer-reviewed journal and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073446.

m6 A mRNA methylation: Biological features, mechanisms, and therapeutic potentials in type 2 diabetes mellitus.

As the most common internal post-transcriptional RNA modification in eukaryotic cells, N6-methyladenosine (m6 A) performs a dynamic and reversible role in a variety of biological processes mediated by methyltransferases (writers), demethylases (erasers), and m6 A binding proteins (readers). M6 A methylation enables transcriptome conversion in different signals that regulate various physiological activities and organ development. Over the past few years, emerging studies have identified that mRNA m6 A regulators defect in ß-cell leads to abnormal regulation of the target mRNAs, thereby resulting in ß-cell dysfunction and loss of ß-cell identity and mass, which are strongly associated with type 2 diabetes mellitus (T2DM) pathogenesis. Also, mRNA m6 A modification has been implicated with insulin resistance in muscles, fat, and liver cells/tissues. In this review, we elaborate on the biological features of m6 A methylation; provide a comprehensive overview of the underlying mechanisms that how it controls ß-cell function, identity, and mass as well as insulin resistance; highlight its connections to glucose metabolism and lipid metabolism linking to T2DM; and further discuss its role in diabetes complications and its therapeutic potentials for T2DM diagnosis and treatment.

Tetraspanin CD63 reduces the progression and metastasis of head and neck squamous cell carcinoma via KRT1-mediated cell cycle arrest.

Despite the fact that metastasis is the leading cause of death in patients with head and neck squamous cell carcinoma, fundamental questions about the mechanisms that enable or inhibit metastasis remain unanswered. Tetraspanin CD63 has been linked to tumor progression and metastasis. However, few studies have examined the role of CD63 in HNSCC. In this study, we discovered that CD63 levels were abnormally altered in HNSCC tissue compared to adjacent tissue (n = 69 pairs), and that this was linked to prognosis. Through functional in vitro and in vivo experiments, the roles of CD63 in HNSCC were confirmed. Overexpression of CD63 inhibited the progression and metastasis of HNSCC cells. Using mass spectrometry and co-immunoprecipitation assays, we discovered that KRT1 could be a direct interacting partner of CD63. Furthermore, both CD63 and KRT1 expression was significantly decreased in metastatic tissue compared with primary tumor tissue (n = 13 pairs), suggesting that CD63 and KRT1 play a role in reducing the metastasis of HNSCC. In summary, we reveal a previously unrecognized role of CD63 in regulating KRT1-mediated cell cycle arrest in HNSCC cells, and our findings contribute to defining an important mechanism of HNSCC progression and metastasis.

Enthesitis-related arthritis: the clinical characteristics and factors related to MRI remission of sacroiliitis.

BACKGROUND: To describe the clinical characteristics and explore the factors related to the MRI remission of sacroiliitis in patients with enthesitis-related arthritis (ERA). METHODS: Patients with ERA from 2018-2022 in our medical center were retrospectively reviewed, which identified according to Pediatric Rheumatology International Trials Organization (PRINTO) criteria. Demographics, clinical characteristics, examinations, and treatments were described. Univariate and multivariate logistic regression models were used to analyze the factors related to MRI remission of sacroiliitis in ERA. RESULTS: This retrospective study included 160 ERA patients (51.9% male) with a mean onset age of 9.2 ± 3.0 years. There were 144 cases (81.9%) with peripheral arthritis, and the hip, knee, and ankle joints were the most commonly involved joints. Enthesitis occurred in 48 cases (30.0%), and sacroiliitis occurred in 142 cases (88.5%) at diagnosis. Human leukocyte antigen (HLA)-B27 was positive in 33 cases (17.1%), and acute uveitis occurred in 3 cases (1.9%). The majority of patients (93.7%) were treated with disease-modifying anti-rheumatic drugs (DMARDs), and 60% with biologics. Among 62 patients with MRI-defined sacroiliitis, 27 (43.5%) cases showed improvement in the sacroiliac joint lesion after treatment. Multivariate logistic regression analysis showed that duration from onset to diagnosis of less than 3 months (OR = 3.609, 95% CI: 1.068-12.192) and active joints of more than 4 (OR = 4.916, 95% CI: 1.006-24.037) were independent factors. CONCLUSION: We highlighted differences in ERA clinical characteristics. Patients with a shorter diagnosis time and more joint involvement improved more significantly in sacroiliac joint lesions after treatment.

Plasma Extracellular Vesicles-Derived miR-99a-5p: A Potential Biomarker to Predict Early Head and Neck Squamous Cell Carcinoma.

Purpose: This study aimed to investigate the applicability of plasma extracellular vesicles (EVs) miR-99a-5p as a potential head and neck squamous cell carcinoma (HNSCC) diagnostic biomarker. Methods: The miRNA expression of HNSCC tissue and plasma EVs were profiled by small RNA sequencing. qRT-PCR was performed to detect miR-99a-5p expression in HNSCC (n = 93) and benign disease (n = 39) plasma EVs and formalin-fixed and paraffin-embedded (FFPE) tissue (n = 110). We constructed receiver-operating characteristic curves to investigate the diagnostic efficiency of plasma EVs miR-99a-5p. Results: Tumor tissue exhibited lower miR-99a-5p than para-tumor tissue. Patients with high miR-99a-5p expression exhibited significantly more p16 positive status. In contrast, HNSCC plasma EVs harbored more miR-99a-5p than the benign disease group. Plasma EVs miR-99a-5p distinguished HNSCC with area under the curve (AUC) of 0.7494 (95% CI: 0.6692-0.8296; p < 0.0001), with 61.54% sensitivity and 75.27% specificity, respectively. Furthermore, plasma EVs miR-99a-5p also distinguished early HNSCC with AUC of 0.7394 (95% CI: 0.6284-0.8504; p = 0.0002), with 79.07% sensitivity and 61.54% specificity, respectively. Conclusion: Plasma EVs miR-99a-5p is a potential biomarker for predicting early HNSCC.

miR-17-5p drives G2/M-phase accumulation by directly targeting CCNG2 and is related to recurrence of head and neck squamous cell carcinoma.

BACKGROUND: The human miR-17-92 polycistron is the first reported and most well-studied onco-miRNA with a cluster of seven miRNAs. miR-17-5p, a member of the miR-17-92 family, plays an important role in tumor cell proliferation, apoptosis, migration and invasion. However, few studies have shown the role of miR-17-5p in the cell cycle of head and neck squamous cell carcinoma (HNSCC). METHODS: RT-qPCR was used to detect miR-17-5p expression levels in 64 HNSCC tissues and 5 cell lines. The relationship between the expression of miR-17-5p in the tissues and the clinical characteristics of the patients was analyzed. HNSCC cells were transfected with an miR-17-5p mimic or inhibitor to evaluate cell cycle distribution by flow cytometry. Cell cycle distribution of cells transfected with target gene was evaluated using flow cytometry. Dual-luciferase reporter assay was used to detect the regulatory effect of miR-17-5p on target gene expression. RESULTS: In the present study, we found that miR-17-5p expression in HNSCC tissues and cell lines was remarkably increased, and miR-17-5p is related to recurrence in HNSCC patients. Silencing miR-17-5p blocked HNSCC cells in G2/M phase, whereas its overexpression propelled cell cycle progression. More importantly, we verified that miR-17-5p negatively regulated CCNG2 mRNA and protein expression by directly targeting its 3'UTR. CONCLUSION: These findings suggest that miR-17-5p might act as a tumor promoter and prognostic factor for recurrence in HNSCC patients.

Small extracellular vesicle-packaged TGFß1 promotes the reprogramming of normal fibroblasts into cancer-associated fibroblasts by regulating fibronectin in head and neck squamous cell carcinoma.

Tumor development and progression hinge upon ongoing coevolution and crosstalk with the tumor microenvironment. In particular, fibroblasts in the tumor stroma are coopted to support tumor growth and survival through interactions with tumor cells. Despite their significant importance, there is no consensus on the origin of cancer-associated fibroblasts (CAFs) in head and neck squamous cell carcinoma (HNSCC). In this study, we demonstrated that small extracellular vesicle (sEV)-packaged TGFß1 can reprogram normal fibroblasts (NFs) into CAFs both in vitro and in vivo. Mechanistically, TGFß1 in sEV activated NFs by regulating fibronectin, rather than modulating the canonical TGFß-Smad signal pathway. Furthermore, TGFß1 and fibronectin are related to HNSCC clinicopathologic features. Plasma sEV TGFß1 may serve as a potential diagnostic biomarker for HNSCC. This hitherto unknown mechanism of reprogramming of NFs into CAFs by a unique pathway has major implications for underlying cancer-recruited stroma responses.

Risk Factors for Left Ventricle Enlargement in Children With Frequent Ventricular Premature Complexes.

We aimed to assess the risk factors for left ventricle (LV) enlargement in children with idiopathic frequent ventricular premature complexes (VPC) and discuss the clinical features and treatment strategies. Children diagnosed with idiopathic frequent VPC at Xinhua Hospital affiliated to the Shanghai Jiao Tong University during 2013 to 2019 were retrospectively evaluated. Gender, age, body mass index, weight, number and sources of frequent VPC, and changes in the LV structure were analyzed and compared. A total of 29 patient showed changes in LV enlargement at diagnosis [age 7.3 ± 4.0 years, 8 (24.1%) had symptoms such as syncope, palpitations, fatigue, and dizziness], whereas 220 showed a normal LV structure [age 7.2 ± 4.5 years, 77 (32.3%) with symptoms]. Patients with LV enlargement showed a higher percentage of VPC on Holter recordings (30.2 ± 10.7 versus 9.4 ± 6.9, p < 0.05), higher prevalence of ventricular tachycardia [22 (75.9%) vs 36 (16.4%), p < 0.0001], higher number of couplets [26 (96.7%) vs 132 (60.0%), p = 0.002], higher number of trigeminy [27 (97.8%) vs 133 (83.2%), p < 0.001], higher QRS wave width [80.0 ± 5.9 vs 77.8 ± 6.8, p = 0.021], and higher incidence of right bundle branch block [11 (37.9%) vs 2 (0.9%), p < 0.001]. Multivariate analysis suggested that right bundle branch block (Odds Ratio = 143.9 p <0.001) and VPC burden (>20%) (Odds Ratio = 132.6, p <0.001) were the risk factors for LV enlargement in children with idiopathic frequent VPC. In conclusion, frequent VPC can induce prominent enlargement or LV dysfunction in children. LV enlargement are reversible after catheter ablation or medication.

Systemic lupus erythematosus gastrointestinal involvement: a computed tomography-based assessment.

Systemic lupus erythematosus (SLE) gastrointestinal (GI) complication is characterized by multi-segment and multi-compartment involvement. The aim of this study is to develop a computed tomography (CT) image-based system for disease evaluation. SLE patients with GI involvement from two independent cohorts were retrospectively included. Baseline abdominal CT scan with intravenous and oral contrast was obtained from each individual. A CT scoring system incorporating the extent of GI tract involvement and intestinal wall thickness, along with extra-GI compartment involvement, was developed and validated. The outcome measurement was the time to GI functional recovery, defined as the time to tolerable per os (PO) intake ≥50% of ideal calories (PO50). A total of 54 and 37 patients with SLE GI involvement were enrolled in the derivation and validation cohorts, respectively. The CT scores for SLE GI involvement were positively correlated with patients' time to PO50 (r = 0.57, p < 0.0001, derivation cohort; r = 0.42, p = 0.0093, validation cohort). Patients with a CT score ≤ 3 had a shorter time to PO50 (median time of 0 day) in pooled cohort, whereas those with a CT score > 3 incurred a significantly prolonged recovery with a median time to PO50 of 13 days (p < 0.0001). The CT-based scoring system may facilitate more accurate assessment and individualized management of SLE patients with GI involvement.

Lack of miR-1246 in small extracellular vesicle blunts tumorigenesis of laryngeal carcinoma cells by regulating Cyclin G2.

Small extracellular vesicle (sEV) has precise impacts on tumor microenvironment and play vital functions in intercellular interaction. However, the functional role of sEV miRNA on laryngeal squamous cell carcinoma (LSCC) is largely unresolved. Here, the expression of miR-1246 in LSCC tissues and plasma sEV was examined. The internalization ability of sEV was determined by uptake assay. Then, the source and purity of sEV were checked through RNase and/or pharmacological inhibitors application. The invasion, migration, proliferation, and cell cycle assays were used to determine the altered abilities of miR-1246 in sEV in LSCC. Finally, target gene of miR-1246, Cyclin G2 (CCNG2), was stained immunohistochemically. In addition, the relationship between CCNG2 and clinicopathological features of patients was analyzed. We found that miR-1246 was higher in LSCC tissues and plasma sEV. MiR-1246 was enriched in sEV rather than soluble form. SEV could be internalized into adjacent cells. Lack of miR-1246 in sEV abrogated the tumorigenesis of LSCC. Furthermore, CCNG2 knockdown arrested the cell cycle and correlated to clinicopathological features and prognosis of LSCC patients. Taken together, we found that the function of sEV miR-1246 by regulating CCNG2 is responsible for LSCC advancement with emphasis on the main source of miR-1246 mainly root in sEV rather than in soluble form.

Predicting medication nonadherence risk in a Chinese inflammatory rheumatic disease population: development and assessment of a new predictive nomogram.

PURPOSE: The aim of this study was to develop and internally validate a medication nonadherence risk nomogram in a Chinese population of patients with inflammatory rheumatic diseases. PATIENTS AND METHODS: We developed a prediction model based on a training dataset of 244 IRD patients, and data were collected from March 2016 to May 2016. Adherence was evaluated using 19-item Compliance Questionnaire Rheumatology. The least absolute shrinkage and selection operator regression model was used to optimize feature selection for the medication nonadherence risk model. Multivariable logistic regression analysis was applied to build a predicting model incorporating the feature selected in the least absolute shrinkage and selection operator regression model. Discrimination, calibration, and clinical usefulness of the predicting model were assessed using the C-index, calibration plot, and decision curve analysis. Internal validation was assessed using the bootstrapping validation. RESULTS: Predictors contained in the prediction nomogram included use of glucocorticoid (GC), use of nonsteroidal anti-inflammatory drugs, number of medicine-related questions, education level, and the distance to hospital. The model displayed good discrimination with a C-index of 0.857 (95% confidence interval: 0.807-0.907) and good calibration. High C-index value of 0.847 could still be reached in the interval validation. Decision curve analysis showed that the nonadherence nomogram was clinically useful when intervention was decided at the nonadherence possibility threshold of 14%. CONCLUSION: This novel nonadherence nomogram incorporating the use of GC, the use of nonsteroidal anti-inflammatory drugs, the number of medicine-related questions, education level, and distance to hospital could be conveniently used to facilitate the individual medication nonadherence risk prediction in IRD patients.