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

Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways. Increasing evidence suggests that imbalances in central nervous system function play an essential role in the progression of visceral pain, but the exact mechanisms underlying the neural circuitry and molecular targets remain largely unexplored. In the present study, the ventral tegmental area (VTA) was shown to mediate visceral pain in mice. Visceral pain stimulation increased c-Fos expression and Ca²⁺ activity of glutamatergic VTA neurons, and optogenetic modulation of glutamatergic VTA neurons altered visceral pain. In particular, the upregulation of NMDA receptor 2A (NR2A) subunits within the VTA resulted in visceral pain in mice. Administration of a selective NR2A inhibitor decreased the number of visceral pain-induced c-Fos positive neurons and attenuated visceral pain. Pharmacology combined with chemogenetics further demonstrated that glutamatergic VTA neurons regulated visceral pain behaviors based on NR2A. In summary, our findings demonstrated that the upregulation of NR2A in glutamatergic VTA neurons plays a critical role in visceral pain. These insights provide a foundation for further comprehension of the neural circuits and molecular targets involved in chronic visceral pain and may pave the way for targeted therapies in chronic visceral pain.
Animals ; Male ; Visceral Pain/metabolism* ; Up-Regulation/physiology* ; Ventral Tegmental Area/metabolism* ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; Neurons/drug effects* ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Chronic Pain/metabolism* ; Glutamic Acid/metabolism*

Patients with periodontal disease often require combined periodontal-orthodontic interventions to restore periodontal health, function, and aesthetics, ensuring both patient satisfaction and long-term stability. Managing these patients involving orthodontic tooth movement can be particularly challenging due to compromised periodontal soft and hard tissues, especially in severe cases. Therefore, close collaboration between orthodontists and periodontists for comprehensive diagnosis and sequential treatment, along with diligent patient compliance throughout the entire process, is crucial for achieving favorable treatment outcomes. Moreover, long-term orthodontic retention and periodontal follow-up are essential to sustain treatment success. This expert consensus, informed by the latest clinical research and practical experience, addresses clinical considerations for orthodontic treatment of periodontal patients, delineating indications, objectives, procedures, and principles with the aim of providing clear and practical guidance for clinical practitioners.
Humans ; Consensus ; Orthodontics, Corrective/standards* ; Periodontal Diseases/complications* ; Tooth Movement Techniques/methods* ; Practice Guidelines as Topic

Diabetic retinopathy, a prevalent and vision-threatening microvascular complication of diabetes mellitus, is the leading cause of blindness among middle-aged and elderly individuals. Natural diterpenoids isolated from Siegesbeckia pubescens demonstrate potent anti-inflammatory properties. This study aimed to identify novel bioactive diterpenoids from S. pubescens and investigate their effects on oxidative stress and inflammatory responses in diabetic retinopathy, both in vitro and in vivo. Three new ent-pimarane-type diterpenoids (1-3) and six known compounds (4-9) were isolated from the aerial parts of S. pubescens. Their structures were elucidated through spectroscopic data interpretation, and absolute configurations were determined by comparing calculated and experimental electronic circular dichroism (ECD) spectra. Among these compounds, 14β,16-epoxy-ent-3β,15α,19-trihydroxypimar-7-ene (5) exhibited the most potent protective effect against high glucose and interleukin-1β (IL-1β)-stimulated human retinal endothelial cells. Mechanistically, compound 5 promoted endothelial cell survival while ameliorating oxidative stress and inflammatory response in diabetic retinopathy, both in vivo and in vitro. These findings not only suggest that diterpenoids such as compound 5 are important anti-inflammatory constituents in S. pubescens, but also indicate that compound 5 may serve as a lead compound for preventing or treating vascular complications associated with diabetic retinopathy.
Diabetic Retinopathy/metabolism* ; Humans ; Oxidative Stress/drug effects* ; Animals ; Diterpenes, Kaurane/administration & dosage* ; Asteraceae/chemistry* ; Male ; Endothelial Cells/drug effects* ; Abietanes/administration & dosage* ; Molecular Structure ; Mice ; Anti-Inflammatory Agents/chemistry* ; Plant Extracts/chemistry* ; Mice, Inbred C57BL

To investigate the bone health status and potential influencing factors of bone mineral density in adult patients with hemophilia, providing a reference for improving their bone health and for the prevention, treatment, and rehabilitation intervention of osteoporosis.

Objective To explore the characteristics and molecular mechanisms of dynamic changes in ovarian function during natural aging in mice.Methods Eighteen female ICR mice of 2,6,10 and 14 months of age(referred to as 2 M,6 M,10 M,and 14 M)were included.The estrous cycle,ovarian index,pregnancy rate and embryo number were detected.The number of follicles was observed using HE staining.Serum anti-Müllerian hormone(AMH)levels were measured using ELISA.Protein and mRNA expression of P16,P21,proliferator-activated receptor-γ coactivator-1α(PGC-1α),and mitochondrial transcription factor A(TFAM)were detected through IHC and qPCR,respectively,and the protein expression of PGC-1α and TFAM was detected by Western blot.Relationships between indicators were evaluated based on Spearman's rank correlation coefficients and logistic regression analyses.Results Compared with estimates in the 2 M group,the percentage of estrous cycle disorders(P＜0.05 in 10 M group,P＜0.01 in 14 M group),ovarian index(P＜0.05 in 10 M group,P＜0.01 in 14 M group),serum AMH level(P＜0.01 in 10 M group,P＜0.01 in 14 M group),number of embryos(P＜0.01 in the 10 M group,P＜0.01 in 14 M group),and pregnancy rate(P＜0.01 in 14 M group)were significantly lower;the number of follicles at all levels and total number of follicles were lower(all P＜0.01),and the number of atretic follicles(all P＜0.01)was higher.Furthermore,P16 and P21 mRNA(P16:P＜0.01 in 10 M and 14 M groups;P21:P＜0.05 in 10 M group,P＜0.01 in 14 M group)and protein levels(P16:P＜0.01 in each group;P21:P＜0.01 in 10 M and 14 M groups)were elevated.Spearman's correlation analyses showed that the age in months was negatively correlated with the ovarian index,serum AMH level,primordial follicle number,number of embryos,and expression of PGC-1αand TFAM and positively correlated with the expression of atretic follicle,P16 and P21(all P＜0.01).Logistic regression analysis revealed a significant negative correlation between the age in months and pregnancy rate(P＜0.01).PGC-1α mRNA was significantly decreased(all P＜0.01),and TFAM mRNA was significantly decreased in 10 M and 14 M groups(P＜0.01).PGC-1α levels were significantly decreased in the 10 M group(IHC:P＜0.05;Western blot:P＜0.01)and 14 M group(all P＜0.01);TFAM levels were significantly lower in 6 M,10 M,and 14 M groups than in the 2 M group(IHC:P＜0.01;Western blot:P＜0.01).Compared with the 2 M group,expression levels of PGC-1α and TFAM were positively correlated with the ovarian index and serum AMH level and negatively correlated with P16 and P21 expression(all P＜0.01).Conclusions Ovarian function in mice declines progressively with age in months,as reflected by reductions in follicles and fertility and the up-regulation of aging markers,which may be associated with the decreased expression of the mitochondrial biogenesis factors PGC-1α and TFAM.

Objective Based on the assumption of spatial heterogeneity,the distribution pattern and risk characteristics of health poverty in middle-aged and elderly people with chronic diseases are described from the perspective of spatial differentiation.In order to providing a theoretical basis for the optimization of subsequent poverty reduction policies and a model policy for other countries.Methods It used factor detector and interaction detector to capture the role of single-factor and multi-factor interactions on the spatial differentiation of health poverty,and risk detectors were utilized to explore the high-risk factors in risky areas Results The single factor explanation of medical assistance and health education activities is prominent,and the factors such as PM2.5,old-age dependency ratio and urban unemployment rate have strong interaction.Furthermore,it identified high-risk factor characteristics in areas at high risk of health poverty.Conclusion The spatial differentiation pattern of health poverty among the middle-aged and elderly chronic disease population in China is the result of the synergistic driving effect of multidimensional factors,and there is variability in the risk characteristics among regions.The government should establish a contextual optimization strategy and pay attention to the joint effect of multiple factors to establish a synergistic management system.

Objective:To evaluate the efficacy and safety of obinutuzumab combined with glucocorticoid-based therapy in patients with relapsed immune thrombotic thrombocytopenic purpura (iTTP).Methods:This study analyzed the efficacy and adverse reactions of four patients with relapsed iTTP who were treated with a combination of obinutuzumab and glucocorticoids to assess the effectiveness and safety of the treatment.Results:All four patients had a history of multiple relapses and had previously undergone treatment with rituximab and bortezomib. Three patients exhibited additional autoantibodies. Following the combined therapy, all patients achieved clinical remission, with ADAMTS13 activity returning to normal levels and inhibitors testing negative. During a median follow-up period of 11 months (range: 3–17 months), all patients maintained sustained remission. No severe adverse events were reported during treatment or follow-up.Conclusion:The combination of obinutuzumab and glucocorticoid-based therapy is effective and safe for treating relapsed iTTP.

Objective To establish a three-dimensional(3-D)structural mode-based nursing quality evaluation index system for the bleeding risk care in patients with deep venous thrombosis(DVT)of lower extremity receiving catheter-directed thrombolysis(CDT),so as to provide a reference for the normalization and standardization of bleeding risk care.Methods Based on the 3-D structural mode,through literature review,clinical practice research and group discussion,the first draft of nursing quality evaluation index system for CDT bleeding risk care was formulated.Using Delphi method,two rounds of letter inquiry were conducted,and the index content and index weighting were determined.Results The nursing quality evaluation index system included 3 level-Ⅰ indicators,11 level-Ⅱ indicators and 58 level-Ⅲ indicators.Two rounds of expert consultation were conducted,with 30 questionnaires for each round.The valid recovery rate of the questionnaire was 100.00％,indicating that expert's enthusiasm was higher.In the first round of letter inquiry,28 experts(93.3％)submitted suggestions for modification,and in the second round of letter inquiry,15 experts(50.0％)submitted suggestions for draft modification.The level of expert authority was as follows:the basis coefficient of expert judgment(Ca)was 0.93,the coefficient of expert familiarity with items(Cs)was 0.90,and the authority coefficient was 0.92.The degree of expert opinion coordination assessed by Kendall's harmony coefficient(Kendall's W)was 0.18-0.26(P＜0.05),and the coefficient of variation of each dimension was less than 0.15.Conclusion The nursing quality evaluation index system established in this study is scientific,reliable and practical.It can provide certain useful reference for the evaluation of CDT bleeding risk care quality.