ABSTRACT
BACKGROUND: Celastrol has been proven effective in anti-inflammatory but was limited in the clinic due to the poor solubility and side effects induced by low bioavailability. Osteoarthritis has acidic and inflammatory environment. Our aim was to load celastrol into HMSNs and capped with chitosan to construct a pH-responsive nanoparticle medicine (CSL@HMSNs-Cs), which is of high solubility for osteoarthritis intra-articular injection treatment. METHODS: The CSL@HMSNs-Cs were assembled and the characteristics were measured. The CSL@HMSNs-Cs was applied in vitro in the chondrocytes collected from rats cartilage tissue and in vivo in the MIA induced knee osteoarthritis rats via intra-articular injection. Cytotoxicity assay, pH-responsive release, pain behavior, MRI, safranin o fast green staining, ELISA and western blot analysis were applied to evaluate the bioavailability and therapeutic effect of CSL@HMSNs-Cs. RESULTS: CSL@HMSNs-Cs was stable due to the protection of the chitosan layers in alkaline environment (pH = 7.7) but revealed good solubility and therapeutic effect in acidic environment (pH = 6.0). The cytotoxicity assay showed no cytotoxicity at relatively low concentration (200 µg/mL) and the cell viability of chondrocytes stimulated by IL-1ß was increased in CSL@HMSNs-Cs group. Paw withdrawal threshold in CSL@HMSNs-Cs group is increased, and MRI and Safranin O Fast Green staining showed improvements in articular surface erosion and joint effusion. The upregulated expression levels of IL-1ß, TNF-α, IL-6, MMP-3 and MMP-13 and NF-κB signaling pathway of chondrocytes were inhibited in CSL@HMSNs-Cs group. CONCLUSION: Hollow mesoporous silica nanoparticles were an ideal carrier for natural drugs with poor solubility and were of high biocompatibility for intra-articular injection. These intra-articular injectable CSL@HMSNs-Cs with improved solubility, present a pH-responsive therapeutic strategy against osteoarthritis.
ABSTRACT
Objectives: To present the temporal changes of CT manifestations in COVID-19 patients from a single fangcang shelter hospital and to facilitate the understanding of the disease course. Materials and Methods: This retrospective study included 98 patients (males: females, 43:55, mean year, 49±12 years) with confirmed COVID-19 at Jianghan fangcang shelter hospital admitted between Feb 05, 2020, and Feb 09, 2020, who had initial chest CTs at our hospital. Radiographic features and CT scores were analyzed. Results: A total of 267 CT scans of 98 patients were evaluated. Our study showed a high median total CT score of 7 within the first week from symptom onset, peaked in the 2nd week at 10, followed by persistently high levels of CT score with 9.5, 7 and 7 for the week 3, 4, and >4, respectively, and a prolonged median disease course (30 days, the median interval between the onset of initial symptoms and discharge). Ground-glass opacity (GGO) (58%, 41/71) was the earliest and most frequent finding in week 1. Consolidation (26%, 14/53) and mixed pattern (40%, 21/53) were predominant patterns in 2nd week. GGO and reticular were the main patterns of later phase CT scans in patients with relatively advanced diseases who had longer illness duration (≥4 weeks). Among the 94 CT abnormalities obtained within 3 days from the twice RT-PCR test turned negative, the mixed pattern was mainly presented in patients with disease duration of 2-3 weeks, for GGO and reticular were common during the whole course. Conclusion: Discharged patients from fangcang shelter hospital demonstrated a high extent of lung abnormalities on CT within the first week from symptom onset, peaked at 2nd week, followed by persistence of high levels and a prolonged median disease course. GGO was the predominant pattern in week 1, consolidation and mixed pattern in 2nd week, whereas GGO and reticular patterns in later stages (≥4 weeks).