Macrophage polarization and energy metabolic reprogramming play pivotal roles in the onset and progression of inflammatory arthritis.Moreover,although previous studies have reported that the proviral integration of Mo...Macrophage polarization and energy metabolic reprogramming play pivotal roles in the onset and progression of inflammatory arthritis.Moreover,although previous studies have reported that the proviral integration of Moloney virus 2(Pim2)kinase is involved in various cancers through the mediation of aerobic glycolysis in cancer cells,its role in inflammatory arthritis remains unclear.In this study,we demonstrated that multiple metabolic enzymes are activated upon Pim2 upregulation during M1 macrophage polarization.Specifically,Pim2 directly phosphorylates PGK1-S203,PDHA1-S300,and PFKFB2-S466,thereby promoting glycolytic reprogramming.Pim2 expression was elevated in macrophages from patients with inflammatory arthritis and collageninduced arthritis(CIA)model mice.Conditional knockout of Pim2 in macrophages or administration of the Pim2 inhibitor HJ-PI01 attenuated arthritis development by inhibiting M1 macrophage polarization.Through molecular docking and dynamic simulation,bexarotene was identified as an inhibitor of Pim2 that inhibits glycolysis and downstream M1 macrophage polarization,thereby mitigating the progression of inflammatory arthritis.For targeted treatment,neutrophil membrane-coated bexarotene(Bex)-loaded PLGA-based nanoparticles(NM@NP-Bex)were developed to slow the progression of inflammatory arthritis by suppressing the polarization of M1 macrophages,and these nanoparticles(NPs)exhibited superior therapeutic effects with fewer side effects.Taken together,the results of our study demonstrated that targeting Pim2 inhibition could effectively alleviate inflammatory arthritis via glycolysis inhibition and reversal of the M1/M2 macrophage imbalance.NM@NPs loaded with bexarotene could represent a promising targeted strategy for the treatment of inflammatory arthritis.展开更多
Objective To evaluate the efficacy of arthroscopic surgery in inflammatory hip arthritis.Methods A retrospective clinical study was conducted inspecting 40 hips in 36 patients of inflammatory arthritis.There were 17 c...Objective To evaluate the efficacy of arthroscopic surgery in inflammatory hip arthritis.Methods A retrospective clinical study was conducted inspecting 40 hips in 36 patients of inflammatory arthritis.There were 17 cases of ankylosing spondylitis,11 cases of rheumatoid arthritis,and 8 cases of psoriatic arthritis.The joints were irrigated and the inflamed tissues were debrided with anthroscopy.The patients were followed up with Harris hip score,Oxford hip score,Visual Analog Scale(VAS),and magnetic resonance imaging(MRI).Statistical analysis was performed using Student t test.Results All of the 36 cases were followed up for 46-103 months,averaging 67.2±8.4 months.Harris and Oxford scores increased from 66.9±12.1 and 69.4±16.4 before operation to 78.4±19.3 and 80.2±18.8 after operation,respectively(P<0.05).VAS score decreased from pre-operative 8.5±2.5 to post-operative 7.2±2.5(P<0.05).All the patients showed improved joint range of motion.MRI revealed alleviation of hip synovitis.The results were classified as excellent in 8 patients,good in 17 patients,fair in 8 patient,and poor in 3 according to Harris hip score.Twenty-seven patients were satisfied with the operative outcomes as they regained normal daily activities.Conclusions Arthroscopy-assisted joint debridement and synovium resection is an effective procedure for hip lesion in inflammatory arthritis.The inflammatory lesion might be thereby controlled and the symptoms be relieved.展开更多
Inflammatory bone diseases constitute a category of chronic inflammatory disorders,with the primary pathological characteristic being the impact of chronic inflammation on bone metabolism and remodeling.It leads to pa...Inflammatory bone diseases constitute a category of chronic inflammatory disorders,with the primary pathological characteristic being the impact of chronic inflammation on bone metabolism and remodeling.It leads to pain,spinal joint deformities,and functional impairments.Common clinical types of inflammatory bone diseases include rheumatoid arthritis,ankylosing spondylitis,and osteoarthritis.However,there is a paucity of effective clinical treatments for inflammatory bone diseases,and pharmacological interventions are frequently associated with intolerable side effects.Traditional Chinese medicine(TCM)has a long-standing history and proven efficacy in managing inflammatory bone diseases.In recent years,an increasing number of studies have highlighted the potential of TCM in this context.This article systematically evaluates the application of TCM in treating inflammatory bone diseases,emphasizing the underlying molecular mechanisms of its anti-inflammatory effects.By elucidating the specific targets of TCM in the treatment of rheumatoid arthritis,ankylosing spondylitis,and osteoarthritis,we aim to provide novel insights into the further exploration of TCM’s role in clinical application for inflammatory bone diseases.展开更多
To the Editor,Gout is a chronic inflammatory arthritis resulting from the deposition of monosodium urate crystals,often presenting as an acute monoarticular flare in the lower extremities.Its incidence continues to ri...To the Editor,Gout is a chronic inflammatory arthritis resulting from the deposition of monosodium urate crystals,often presenting as an acute monoarticular flare in the lower extremities.Its incidence continues to rise globally,paralleling increasing rates of obesity and metabolic disorders.Known risk factors include obesity,hypertension,diuretic use,chronic kidney disease,high fructose consumption,and diets rich in purines.1 Type 2 diabetes mellitus(T2DM),especially when diagnosed early,has also been implicated in raising the risk of gout,likely due to shared metabolic and inflammatory pathways.2 While conventional therapies for gout center on urate‐lowering strategies and flare prevention,recent interest has emerged around how newer antidiabetic medications might modulate gout risk.展开更多
基金supported by the National Natural Science Foundation of China(No.82172385 to HS)National Natural Science Foundation of China(No.82172349 to YW)+4 种基金Guangdong Provincial Clinical Research Center for Orthopedic Diseases(No.2023B110001 to HS)Futian Healthcare Research Project(No.FTWS2022020 to JL)Futian Healthcare Research Project(No.FTWS2023058 to JL)Guangdong Natural Science Foundation(No.2023A1515010531 to JL)Shenzhen Science and Technology Program(No.KCXFZ20230731092959001 to PW).
文摘Macrophage polarization and energy metabolic reprogramming play pivotal roles in the onset and progression of inflammatory arthritis.Moreover,although previous studies have reported that the proviral integration of Moloney virus 2(Pim2)kinase is involved in various cancers through the mediation of aerobic glycolysis in cancer cells,its role in inflammatory arthritis remains unclear.In this study,we demonstrated that multiple metabolic enzymes are activated upon Pim2 upregulation during M1 macrophage polarization.Specifically,Pim2 directly phosphorylates PGK1-S203,PDHA1-S300,and PFKFB2-S466,thereby promoting glycolytic reprogramming.Pim2 expression was elevated in macrophages from patients with inflammatory arthritis and collageninduced arthritis(CIA)model mice.Conditional knockout of Pim2 in macrophages or administration of the Pim2 inhibitor HJ-PI01 attenuated arthritis development by inhibiting M1 macrophage polarization.Through molecular docking and dynamic simulation,bexarotene was identified as an inhibitor of Pim2 that inhibits glycolysis and downstream M1 macrophage polarization,thereby mitigating the progression of inflammatory arthritis.For targeted treatment,neutrophil membrane-coated bexarotene(Bex)-loaded PLGA-based nanoparticles(NM@NP-Bex)were developed to slow the progression of inflammatory arthritis by suppressing the polarization of M1 macrophages,and these nanoparticles(NPs)exhibited superior therapeutic effects with fewer side effects.Taken together,the results of our study demonstrated that targeting Pim2 inhibition could effectively alleviate inflammatory arthritis via glycolysis inhibition and reversal of the M1/M2 macrophage imbalance.NM@NPs loaded with bexarotene could represent a promising targeted strategy for the treatment of inflammatory arthritis.
文摘Objective To evaluate the efficacy of arthroscopic surgery in inflammatory hip arthritis.Methods A retrospective clinical study was conducted inspecting 40 hips in 36 patients of inflammatory arthritis.There were 17 cases of ankylosing spondylitis,11 cases of rheumatoid arthritis,and 8 cases of psoriatic arthritis.The joints were irrigated and the inflamed tissues were debrided with anthroscopy.The patients were followed up with Harris hip score,Oxford hip score,Visual Analog Scale(VAS),and magnetic resonance imaging(MRI).Statistical analysis was performed using Student t test.Results All of the 36 cases were followed up for 46-103 months,averaging 67.2±8.4 months.Harris and Oxford scores increased from 66.9±12.1 and 69.4±16.4 before operation to 78.4±19.3 and 80.2±18.8 after operation,respectively(P<0.05).VAS score decreased from pre-operative 8.5±2.5 to post-operative 7.2±2.5(P<0.05).All the patients showed improved joint range of motion.MRI revealed alleviation of hip synovitis.The results were classified as excellent in 8 patients,good in 17 patients,fair in 8 patient,and poor in 3 according to Harris hip score.Twenty-seven patients were satisfied with the operative outcomes as they regained normal daily activities.Conclusions Arthroscopy-assisted joint debridement and synovium resection is an effective procedure for hip lesion in inflammatory arthritis.The inflammatory lesion might be thereby controlled and the symptoms be relieved.
文摘Inflammatory bone diseases constitute a category of chronic inflammatory disorders,with the primary pathological characteristic being the impact of chronic inflammation on bone metabolism and remodeling.It leads to pain,spinal joint deformities,and functional impairments.Common clinical types of inflammatory bone diseases include rheumatoid arthritis,ankylosing spondylitis,and osteoarthritis.However,there is a paucity of effective clinical treatments for inflammatory bone diseases,and pharmacological interventions are frequently associated with intolerable side effects.Traditional Chinese medicine(TCM)has a long-standing history and proven efficacy in managing inflammatory bone diseases.In recent years,an increasing number of studies have highlighted the potential of TCM in this context.This article systematically evaluates the application of TCM in treating inflammatory bone diseases,emphasizing the underlying molecular mechanisms of its anti-inflammatory effects.By elucidating the specific targets of TCM in the treatment of rheumatoid arthritis,ankylosing spondylitis,and osteoarthritis,we aim to provide novel insights into the further exploration of TCM’s role in clinical application for inflammatory bone diseases.
文摘To the Editor,Gout is a chronic inflammatory arthritis resulting from the deposition of monosodium urate crystals,often presenting as an acute monoarticular flare in the lower extremities.Its incidence continues to rise globally,paralleling increasing rates of obesity and metabolic disorders.Known risk factors include obesity,hypertension,diuretic use,chronic kidney disease,high fructose consumption,and diets rich in purines.1 Type 2 diabetes mellitus(T2DM),especially when diagnosed early,has also been implicated in raising the risk of gout,likely due to shared metabolic and inflammatory pathways.2 While conventional therapies for gout center on urate‐lowering strategies and flare prevention,recent interest has emerged around how newer antidiabetic medications might modulate gout risk.
