OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Cadmium is one of the heavy metals with severe reproductive toxicity,whose half-life lasts 20 to 40 years.Cadmium could induce dysfunction of testis and epididymis for its significant accumulation in human testis,and the amount,motility parameters and morphology of sperm change abnormally.The adverse change could also extend to male offspring and cause the impairment of their reproductive system.There has been no clear mecha-nism of how cadmium induces dysfunction of male reproductive system,and treatment for the adverse influence on male reproductive system by cadmium has not yet been found.Therefore,this problem has been discussed in repro-ductive and environmental field for a long time.A number of previous investigations showed that cadmium could damage male fertility by followed pathways,including interfering with hormone secretion,inducing oxidative stress,activating inflammation and apoptosis,and causing energy metabolism disorder,etc.In order to enlighten new ideas for therapeutic targets of male reproductive function damage induced by cadmium,we systematically reviewed and summarized the findings of previous publications in this paper.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1(Keap1)and the nucleation of nuclear factor erythroid 2-related factor 2(Nrf2)by up-regulating the expression of sestrin 2(SESN2)in endothelial cells,thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1(Keap1)and the nucleation of nuclear factor erythroid 2-related factor 2(Nrf2)by up-regulating the expression of sestrin 2(SESN2)in endothelial cells,thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1(Keap1)and the nucleation of nuclear factor erythroid 2-related factor 2(Nrf2)by up-regulating the expression of sestrin 2(SESN2)in endothelial cells,thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1(Keap1)and the nucleation of nuclear factor erythroid 2-related factor 2(Nrf2)by up-regulating the expression of sestrin 2(SESN2)in endothelial cells,thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1(Keap1)and the nucleation of nuclear factor erythroid 2-related factor 2(Nrf2)by up-regulating the expression of sestrin 2(SESN2)in endothelial cells,thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1(Keap1)and the nucleation of nuclear factor erythroid 2-related factor 2(Nrf2)by up-regulating the expression of sestrin 2(SESN2)in endothelial cells,thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1(Keap1)and the nucleation of nuclear factor erythroid 2-related factor 2(Nrf2)by up-regulating the expression of sestrin 2(SESN2)in endothelial cells,thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1(Keap1)and the nucleation of nuclear factor erythroid 2-related factor 2(Nrf2)by up-regulating the expression of sestrin 2(SESN2)in endothelial cells,thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.