BACKGROUND: Osteoarthritis (OA) is a prevalent joint disorder that significantly impairs quality of life among elderly individuals because of chronic pain and physical disability. As the global burden of OA continues to rise, novel therapeutic strategies are urgently needed. Kaempferide (KA), a flavonoid derived from traditional Chinese herbal medicine, is known for its anti-inflammatory properties. However, the effect of KA on the progression of OA has not been well investigated. This study aimed to explore the therapeutic potential of KA in an OA model and investigate the underlying mechanisms via transcriptomic sequencing. METHODS: An in vitro OA model was established using SW1353 cells treated with interleukin-1 beta (IL-1β) and different concentrations of KA (30, 60, or 90 μmol/L) for 24 h. The anti-inflammatory effects of KA were assessed using quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blotting. In vivo , a papain-induced OA rat model was used to evaluate the therapeutic effects of KA through histological and behavioral analyses. Transcriptomic sequencing was performed to explore the differentially expressed genes (DEGs) and related signaling pathways. Statistical analysis was conducted using one-way analysis of variance. RESULTS: KA significantly increased cell viability in the OA chondrocyte model and downregulated the expression of inflammatory cytokines and cartilage degradation markers, with the greatest reduction observed at 90 μmol/L. In vivo , KA treatment mitigated cartilage degradation and improved gait behavior in OA rats. Transcriptomic analysis revealed substantial modulation of DEGs, implicating the hypoxia-inducible factor-1 (HIF-1) signaling pathway as a key mechanism. Further blocking and rescue experiments revealed that KA regulated key molecules within the HIF-1 pathway, specifically interferon-gamma (IFN-γ) and hypoxia-inducible factor 1-alpha (HIF-1α), confirming their critical roles in mediating the therapeutic effects of KA. CONCLUSION KA inhibited the progression of OA by targeting the HIF-1 signaling pathway, reducing inflammation, and cartilage degradation.
Animals ; Osteoarthritis/metabolism* ; Signal Transduction/drug effects* ; Rats ; Rats, Sprague-Dawley ; Humans ; Male ; Hypoxia-Inducible Factor 1/metabolism* ; Interleukin-1beta

Objective:To explore the morphology of coronoid process fracture in terrible triad injury based on Adams classification.Methods:A retrospective cross-sectional study was used to analyze the three-dimensional CT data of 51 patients with terrible trind injury treated at First Affiliated Hospital of Fujian Medical University from January 2013 to August 2021, including 33 males and 18 females, aged 18-88 years [(44.7±12.0)years]. The model of ulna coronoid process fracture was established by three-dimensional CT reconstruction technology and was classified according to Adams coronoid process fracture classification. Type I was the coronoid process tip fracture, type II the coronoid process transverse fracture, type III the base fracture of the coronoid process, type IV anterior internal fracture the anteromedial oblique fracture of the coronoid process, and type IV anterior external fracture the anterolateral oblique fracture of the coronoid process. According to the characteristics of the coronoid fracture fragment, type IV anterior external fracture was divided into two subtypes: α subtype involving the coronoid tip and β subtype without involving the coronoid tip. Then, the proportion, height, surface area and volume of different types of coronoid fractures were measured. The proportion, height, surface area and volume of fracture fragments of two subtypes of type IV anterior external fracture were measured, as well as the area of ulnar trochlear joint, area of trochlear joint of ulnar fracture fragment, proportion of the area of trochlear joint affected by the ulnar fragment, area of proximal radioulnar joint, area of proximal radioulnar joint of ulnar fracture fragment and proportion of the area of proximal radioulnar joint affected by the ulnar fragment.Results:Among the patients with terrible triad injury, the ulnar coronoid process fracture was Adams type I in 17 patients (33%), type II in 4 (8%), type III in 4 (8%), type IV anterior internal fracture in 4 (8%) and type IV anterior external fracture in 22 (43%). The height of fracture fragment of type I, type II, type III, type IV anterior internal fracture and type IV anterior external fracture was (3.7±1.9)mm, (10.8±1.1)mm, (14.4±1.2)mm, (5.2±2.4)mm and (6.7±2.6)mm, respectively; the surface area was 63.7(21.4, 221.0)mm 2, 1 086.8(606.8, 1 434.2)mm 2, 1 658.8(1 335.6, 1 695.4)mm 2, 437.3(185.6, 437.3)mm 2 and 511.8(198.8, 646.5)mm 2, respectively; the volume was 46.3(21.4, 180.5)mm 3, 938.7(629.8, 1 011.3)mm 3, 1 797.4(1 520.2, 1 903.7)mm 3, 429.3(138.1, 992.4)mm 3 and 461.9(144.9, 707.1)mm 3, respectively. There were significant differences in the height, surface area and volume of coronoid process fracture with different Adams classification (all P<0.01). Among 22 patients with type IV anterior external fracture, 12 patients were with α subtype and 10 with β subtype. The fracture height of α and β subtypes was (8.6±2.6)mm and (5.0±2.4)mm, respectively; the surface area was 633.2 (530.3, 727.4)mm 2 and 181.4 (136.7, 450.3)mm 2, respectively; the volume was 692.8 (477.6, 778.0)mm 3 and 128.0 (74.2, 405.1)mm 3, respectively. The height, surface area and volume of fracture fragment were significantly different between the two subtypes (all P<0.01). The area of ulnar trochlear joint of α and β subtypes were 901.4(755.1, 1 060.6)mm 2 and 835.2(767.7,909.3)mm 2, respectively; the area of trochlear joint of α and β subtype fragment was 104.1(79.4, 139.9)mm 2 and 38.8(21.3, 58.1)mm 2, respectively; the proportion of the area of trochlear joint affected by α and β subtype fragment was 0.12(0.09, 0.15) and 0.05(0.03, 0.07), respectively. There was no significant difference between α and β subtypes in the area of trochlear joint of ulna ( P>0.05), but the area of trochlear joint of α subtype fragment and proportion of the area of trochlear joint affected by α subtype fragment were higher than those of β subtype fragment (all P<0.01). The area of proxima radioulnar joint of α and β subtypes was 147.9(111.7,164.2)mm 2 and 137.0(118.7,166.7)mm 2, respectively; the area of proximal radioulnar joint of α and β subtypes fragment was 17.7(13.4, 52.2)mm 2 and 6.1(2.6, 20.0)mm 2, respectively; the proportion of the area of proximal radioulnar joint affected by α and β subtypes fragment was 0.12(0.10, 0.35) and 0.05(0.03, 0.15), respectively. There were no significant differences between the two subtypes in proximal radioulnar joint damage (all P>0.05). Conclusions:Adams type IV fracture of the coronoid process of the ulna occupies a large proportion in terrible triad injury, and the type IV anterior external fracture is the main type containing two subtypes with differences in fragment size and shape. However, the injuries to the proximal radioulnar joint surface are similar for the two subtypes, so the injuries of type IV anterior external fracture with different sizes to the proximal radioulnar joint surface should not be neglected in clinical treatment.

Objective:To analyze the types of ulnar coronoid process fractures in terrible triad injury (TTI) using three coronoid fracture classification systems and to explore the characteristics of coronoid process fractures and compare the reliability of different coronoid process fractures classification systems in TTI.Methods:A retrospective case series study was used to analyze the CT data of 43 patients with typical TTI admitted to First Affiliated Hospital of Fujian Medical University from January 2013 to October 2020. There were 26 males and 17 females, aged from 18 to 88 years [(41.8±15.6)years]. An independent three-dimensional model of the proximal ulna was established using the CT three-dimensional reconstruction technology. The characteristics of the coronoid process fractures were observed. The Regan-Morrey classification, O'Driscoll classification and Adams classification were used to classify the ulnar coronoid process fractures. The reliability of the three classification systems of coronoid fractures was analyzed.Results:The fracture line of the coronoid process was mostly located anterolaterally. Among all patients with ulnar coronoid fractures, there were 17 patients (40%) with type I, 19 (44%) with type II and 7(16%) with type III according to Regan-Morrey classification; there were 34 patients (79%) with type I, 2(5%) with type II and 7(16%) with type III according to O'Driscoll classification; there were 12 patients (28%) with type I, 3(7%) with type II, 7(16%) with type III, 18(42%) with type IV AL and 2(5%) with type IV AM according to Adams classification. Through reliability analysis, the Kappa coefficients of the inter-observer and intra-observer 1, 2, 3 of Regan-Morrey classification were 0.752, 0.813, 0.772 and 0.703, respectively; the Kappa coefficients of the inter-observer and intra-observer 1, 2, 3 of O'Driscoll classification were 0.797, 0.774, 0.837 and 0.775, respectively; the Kappa coefficients of the inter-observer and intra-observer 1, 2, 3 of Adams classification were 0.805, 0.835, 0.837 and 0.875, respectively.Conclusions:Most of the coronoid process fractures locate anterolaterally in TTI. Compared with Regan-Morrey classification and O'Driscoll classification, the reliability of Adams classification is best. Adams classification further subdivides the anterolateral fractures of the coronoid process, which may be more suitable in evaluating the classification of ulnar coronoid process fractures in TTI.

Objective:To explore the characteristics and advantages of Whole-Mounting immnunofluorescent staining and laser speckle flow imaging technology in the vascular imaging of mouse ear extended flap.Methods:In this study, total of 25 ICR mice were included.Ten ICR mice were cut off the middle and lateral angiosome to establish an extended flap model, and 3 days later, the changes in the blood supply of the ear flap were observed. The ear area , tissue layer thickness and blood vessel distribution in the healthy side were observed at the same time.Obtain the mouse ears 3 days after modeling, and dissect them into three layers, i.e, the anterior skin layer , the cartilage layer and the posterior skin layer. The distribution and morphology of blood vessels, nerves and monocytes/macrophages in the anterior skin layer were stained and detected by the whole-mount immunofluorescence staining.Ten mice were adopted and an incision was made through the ear horizontally above the bifurcation of the middle angiosome of the mouse ear to establish a delayed extended flap model. Then the blood flow changes in the mouse ear were observed by laser speckle flow imaging andt he blood perfusion values were recorded immediately, 1 d, 2 d, 3 d and 4 d after the operation, respectively.Results:The area of the mouse ear was about 1.3 cm 2 , the thickness was about (0.16±0.04) mm, and the blood was supplied by three vascular bundles: the lateral caudal vascular bundle, the middle vascular bundle and the medial cephalic vascular bundle. The thickness of the anterior and posterior skin and cartilage of the mouse ears were (88±5)μm, (41±3)μm and (29±2)μm, respectively. The whole-mount immunofluorescence staining results clearly showed that the diameter of small vessels in the choke area was (50 ± 6) μm on the third day after modeling. It could be seen that the nerve and artery in mouse ear were in concomitant relationship and the nerve segment attached to the surface of the artery without obvious accompany or clinging to the vein. There were a large number of monocyte macrophages distributed in clusters in the dilated and curved arteries, but they were only scattered outside the artery. Laser speckle flow imaging results showed that there were (6 ± 2) transverse vessels in each auricular flap, and the diameter and blood flow increased significantly in the delayed extended earflap model. Immediately after the operation and at 1d, 2d, 3d, and 4d, the average blood perfusion values of transverse vessels were (92±11) PU, (136±26) PU, (147±27) PU and (176±27) PU, respectively. Conclusions:The Whole-Mounting immnunofluorescent staining and the laser speckle blood flow imaging technology can be used to well observe the blood vessels, nerves, mononuclear macrophages and blood flow perfusion of the mouse extended flap, which can play an important role in the study of blood supply of mouse extended flap.

Objective:To explore the characteristics and advantages of Whole-Mounting immnunofluorescent staining and laser speckle flow imaging technology in the vascular imaging of mouse ear extended flap.Methods:In this study, total of 25 ICR mice were included.Ten ICR mice were cut off the middle and lateral angiosome to establish an extended flap model, and 3 days later, the changes in the blood supply of the ear flap were observed. The ear area , tissue layer thickness and blood vessel distribution in the healthy side were observed at the same time.Obtain the mouse ears 3 days after modeling, and dissect them into three layers, i.e, the anterior skin layer , the cartilage layer and the posterior skin layer. The distribution and morphology of blood vessels, nerves and monocytes/macrophages in the anterior skin layer were stained and detected by the whole-mount immunofluorescence staining.Ten mice were adopted and an incision was made through the ear horizontally above the bifurcation of the middle angiosome of the mouse ear to establish a delayed extended flap model. Then the blood flow changes in the mouse ear were observed by laser speckle flow imaging andt he blood perfusion values were recorded immediately, 1 d, 2 d, 3 d and 4 d after the operation, respectively.Results:The area of the mouse ear was about 1.3 cm 2 , the thickness was about (0.16±0.04) mm, and the blood was supplied by three vascular bundles: the lateral caudal vascular bundle, the middle vascular bundle and the medial cephalic vascular bundle. The thickness of the anterior and posterior skin and cartilage of the mouse ears were (88±5)μm, (41±3)μm and (29±2)μm, respectively. The whole-mount immunofluorescence staining results clearly showed that the diameter of small vessels in the choke area was (50 ± 6) μm on the third day after modeling. It could be seen that the nerve and artery in mouse ear were in concomitant relationship and the nerve segment attached to the surface of the artery without obvious accompany or clinging to the vein. There were a large number of monocyte macrophages distributed in clusters in the dilated and curved arteries, but they were only scattered outside the artery. Laser speckle flow imaging results showed that there were (6 ± 2) transverse vessels in each auricular flap, and the diameter and blood flow increased significantly in the delayed extended earflap model. Immediately after the operation and at 1d, 2d, 3d, and 4d, the average blood perfusion values of transverse vessels were (92±11) PU, (136±26) PU, (147±27) PU and (176±27) PU, respectively. Conclusions:The Whole-Mounting immnunofluorescent staining and the laser speckle blood flow imaging technology can be used to well observe the blood vessels, nerves, mononuclear macrophages and blood flow perfusion of the mouse extended flap, which can play an important role in the study of blood supply of mouse extended flap.

0.05). However, monocrotaline significantly increased WT% and WA% of pulmonary arterioles (WT:39.1%?2.8% vs 50.8%?3.1%, WA:51.2%?3.0% vs 74.5%?2.9%, P