Volume 11, Issue 1

The pathogenesis of connective tissue diseases (CTDs), represented by systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), primary Sjögren’s syndrome (pSS), and idiopathic inflammatory myopathies (IIM), includes various immune cells involved in both innate and adaptive immunity. The mesenchymal stem cells (MSCs) are unique due to their regulatory effect on immunity. This makes them a promising therapeutic approach for patients with immune-mediated disorders such as CTD. The safety and clinical efficacy of MSC treatment in CTD have been tested in a growing number of preclinical and clinical studies. Administration of MSCs has consistently shown benefits with both symptomatic and histologic improvement in CTD animal models. MSC therapies in severe and drug-resistant CTD patients have shown promise in a number of the pilot studies, cohort studies, and randomized controlled trials in SLE, RA, and SSc, but some problems still need to be resolved in the transition from the bench to the bedside. The relevant studies in pSS and IIM are still in their infancy, but have displayed encouraging outcomes. Considerable efficacy variations have been observed in terms of the route of delivery, time of MSC injection, origin of the MSCs and dosage. Furthermore, the optimization of conventional drugs combined with MSC therapies and the applications of novel cell engineering approaches requires additional research. In this review, we summarize the current evidence about the immunoregulatory mechanism of MSCs, as well as the preclinical and clinical studies of MSC-based therapy for the treatment of CTDs.

The idiopathic inflammatory myopathies (IIMs) are a group of connective tissue diseases that afect multiple organ systems, including the lungs. Interstitial lung disease (ILD) is the most common and heterogeneous complication of IIMs, with its degree ranging from mild to fatal. Thus, it is critical to identify clinical features and validated biomarkers for predicting disease progression and prognosis, which could be beneficial for therapy adjustment. In this review, we discuss predictors for rapid progression of IIM-ILD and propose guidance for disease monitoring and implications of therapy. Systematic screening of myositis-specific antibodies, measuring serum biomarker levels, pulmonary function tests, and chest high-resolution computer tomography will be beneficial for the evaluation of disease progression and prognosis.

Background and Objectives Moderate-intensity continuous training (MICT) is used to observe lipidomic effects in adults. However, the efects of MICT on lipid metabolism in adolescents remain unclear. Therefore, we aimed to longitudinally characterize the lipid profile in adolescents during different periods of 6-week MICT. Methods Fifteen adolescents undertook bicycle training at 65% of maximal oxygen consumption. Plasma samples were collected at four time points (T0, T1, T2, and T3). Targeted lipidomics was assessed by ultra-performance liquid chromatography–tandem mass spectrometry to characterize the plasma lipid profiles of the participants to identify the lipids present at differing concentrations and changes in lipid species with time. Results MICT afected the plasma lipid profiles of the adolescents. The concentrations of diglycerides, phosphatidylinositol, lysophosphatidic acid, lysophosphatidylcholine, and lysophosphatidylethanolamine were increased at T1, decreased at T2, and increased again at T3. Fatty acids (FAs) showed an opposite trend. Ether-linked alkylphosphatidylcholine and triglycerides were significantly increased and remained high. Sphingolipid concentrations initially decreased and then remained low. Therefore, a single bout of exercise had substantial efects on lipid metabolism, but by T3, fewer lipid species were present at significantly diferent concentrations and the magnitudes of the remaining diferences were smaller than those at earlier times. Among all the changed lipids, only DG(14:1/18:1), HexCer(d18:1/22:1) and FA(22:0) showed no significant correlations with any other 51 lipids ( P < 0.05). Glycerides and phospholipids showed positive correlations with each other ( P < 0.05), but FAs were significantly negatively correlated with glycerides and phospholipids while positively with other FAs ( P < 0.05). Pathway enrichment analysis showed that 50% of the metabolic pathways represented were related to lipid metabolism and lipid biosynthesis. Conclusion MICT increases ether-linked alkylphosphatidylcholine and triglyceride concentrations. Diglyceride, phosphatidylinositol, and lysophosphatidylcholine concentrations initially rise and then decrease 6 weeks after MICT, but FA concentrations show an opposite trend. These changes might correlate with lipid metabolism or biosynthesis pathways.

Background and Objectives Transcutaneous point-of-care ultrasound (POCUS) is a good tool to monitor the trachea in many clinical practices. The aim of our study is to verify the feasibility of POCUS-guided submucosal injection as a potential drug delivery method for the treatment of tracheal stenosis. Materials and methods The inner wall of the trachea was monitored via a bronchoscope during the POCUS-guided submucosal injection of methylene blue in fresh ex vivo porcine trachea to evaluate the distribution of methylene blue. The feasibility and eficacy of POCUS-guided submucosal injection were evaluated in a tracheal stenosis rabbit model. Animals were divided into sham group, tracheal stenosis group, and treatment group. Ten days after the scraping of the tracheal mucosa or sham operation, POCUS-guided submucosal injection of paclitaxel or saline was performed. Seven days after the submucosal injection, the trachea was assessed by cervical computed tomography (CT) scan and ultrasound. Results The distribution of methylene blue in trachea proved the technical feasibility of POCUS-guided submucosal injection. CT evaluation revealed that the tracheal stenosis index and the degree of tracheal stenosis increased significantly in the stenosis group, while POCUS-guided submucosal injection of paclitaxel partially reversed the tracheal stenosis. POCUS-guided submucosal injection of paclitaxel also decreased the lamina propria thickness and collagen deposition in the stenosed trachea. Conclusion POCUS-guided submucosal paclitaxel injection alleviated tracheal stenosis induced by scraping of the tracheal mucosa. POCUS-guided submucosal injection might be a potential method for the treatment of tracheal stenosis.

Objectives Childhood obesity affects multiple organs in the body and is associated with both significant morbidity and ultimately premature mortality. Childhood obesity, especially dyslipidemia, can lead to early atherosclerosis and premature cardiovascular disease (CVD) in adulthood. The detection of exhaled volatile organic compounds (VOCs) in the breath offers the opportunity for the discovery of novel disease-specific biomarkers. This study aimed to identify VOCs that correlate with childhood obesity accompanied by dyslipidemia. Methods A total of 82 overweight or obese children between the ages of 8 and 12 years were recruited from the exercise on obesity adolescents in Peking (EXCITING) study (NCT04984005). The breath VOCs of the participants were measured by gas chromatography-mass spectrometry (GC-MS). The classification was performed using principal component analysis (PCA) of the relative abundance of VOCs. The difference between the obese and overweight groups with or without dyslipidemia was analyzed. Results Among the 82 children, 25 were overweight, of whom 10 had dyslipidemia. The other 57 children were obese, and 17 of them had dyslipidemia. Obese children with dyslipidemia had higher triglycerides and elevated non–high-density lipoprotein-cholesterol compared to overweight children without dyslipidemia. We confirmed 13 compounds based on database well matches (average score > 80) for mass spectra and refractive index. These 13 VOCs were grouped into three chemical functional groups: saturated hydrocarbons, aromatic hydrocarbons and unsaturated aldehydes. For obese children with dyslipidemia, the PCA scatter plot of the three chemical groups was obviously separated from the other groups. Some of the candidates, including heptadecane, naphthalene, and cis -6-nonnenol, were significantly higher in obese children with dyslipidemia than in overweight groups with or without dyslipidemia. Conclusion A suite of VOCs from three chemical function groups, saturated hydrocarbons, aromatic hydrocarbons, and unsaturated aldehydes, were separated in the obese children with dyslipidemia. Heptadecane, naphthalene, and cis -6-nonenol were significantly elevated in obese children with dyslipidemia. Our findings underscore the potential value of the candidate VOCs for future risk categorization.