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

Objective To investigate the effects of laparoscopic sleeve gastrectomy(LSG)on the cardiac structure and function in obese patients with heart failure(HF)and compare the efficacy of LSG across obese patients with different HF types.Methods This study included 33 obese patients with HF who underwent LSG.The clinical indicators were compared between before operation and 12 months after operation.Repeated measures analysis of variance was employed to evaluate the changes in echocardiographic parameters before operation and 3,6,and 12 months after operation.Patients were allocated into a HF with preserved ejection fraction group(n=17),a HF with mildly reduced ejection fraction group(n=5)and a HF with reduced ejection fraction(HFrEF)group(n=11)based on left ventricular ejection fraction(LVEF)before operation for subgroup analyses of the effects of LSG on the cardiac structure and function of obese patients with HF.The paired samples t-test was conducted to assess the degree of cardiac structural and functional alterations after LSG.Results The 33 patients included 69.7% males,with an average age of(35.3±9.9)years,and a body mass index(BMI)of(51.2±9.8)kg/m².The median follow-up was 9.0(5.0,13.3)months.Compared with the preoperative values,the postoperative BMI(P=0.002),body surface area(BSA)(P=0.009),waist circumference(P=0.010),hip circumference(P=0.031),body fat content(P=0.007),and percentage of patients with cardiac function grades Ⅲ-IV(P<0.001)decreased.At the 12-month follow-up left atrial diameter(P=0.006),right atrial long-axis inner diameter(RAD1)(P<0.001),right atrial short-axis inner diameter(RAD2)(P<0.001),right ventricular inner diameter(P=0.002),interventricular septal thickness at end-diastolic(P=0.002),and left ventricular end-diastolic volumes(P=0.004)and left ventricular end-systolic volumes(P=0.003) all significantly reduced compared with preoperative values.Additionally,left ventricular fractional shortening and LVEF improved(both P<0.001).Subgroup analyses revealed that cardiac structural parameters significantly decreased in the HF with preserved ejection fraction,HF with mildly reduced ejection fraction,and HFrEF subgroups compared with preoperative values.Notably,the HFrEF group demonstrated the best performance in terms of left atrial diameter(P=0.003),left ventricular inner diameter at end-diastole(P=0.008),RAD1(P<0.001),RAD2(P=0.004),right ventricular inner diameter(P=0.019),left ventricular end-diastolic volume(P=0.004)and left ventricular end-systolic volume(P=0.001),cardiac output(P=0.006),tricuspid regurgitation velocity(P=0.002),and pulmonary artery systolic pressure(P=0.001) compared to preoperatively.Postoperative left ventricular fractional shortening(P<0.001,P=0.003,P<0.001)and LVEF(P<0.001,P=0.011,P=0.001)became higher in all the three subgroups than the preoperative values.Conclusions LSG decreased the body weight,BMI,and BSA,improved the cardiac function grade,reversed the enlargement of the left atrium and left ventricle,reduced the right atrium and right ventricle,and enhanced the left ventricular systolic function.It was effective across obese patients with different HF types.Particularly,LSG demonstrates the best performance in improving the structures of both atria and ventricles in obese patients with HFrEF.
Humans ; Male ; Female ; Gastrectomy/methods* ; Heart Failure/complications* ; Adult ; Obesity/physiopathology* ; Laparoscopy ; Middle Aged ; Heart/physiopathology* ; Stroke Volume

The therapeutic effects of Yueju Pills on depression and cardiovascular diseases have been widely recognized. Previous studies have shown that the drug can significantly improve depressive-like behaviors induced by chronic unpredictable mild stress(CUMS) combined with atherosclerosis(AS). Given the complex pathogenesis of psychocardiac diseases, this study integrated metabolomics and network pharmacology to systematically elucidate the mechanism of Yueju Pills in alleviating depressive symptoms in psychocardiac diseases. The results demonstrate that, after Yueju Pill intervention, the levels of 9 abnormal metabolites in the hippocampus restore to normal ranges, primarily involving key pathways or signaling pathways, including the cyclic adenosine monophosphate(cAMP), mammalian target of rapamycin(mTOR), glycine/serine/threonine metabolism, and aminoacyl-tRNA biosynthesis. In a high-fat diet-induced CUMS ApoE~(-/-) mouse model, Yueju Pills significantly increases adenosine monophosphate(AMP) levels and decreases L-alanine and D-glyceric acid levels in the hippocampus. In conclusion, Yueju Pills exert antidepressant effects by regulating multiple metabolic axes, including glycine/serine/threonine metabolism and the cAMP, mTOR signaling pathways. Network pharmacology predictions reveal that the treatment of CUMS combined with AS by its core active components may be realized through modulating pathways concerning neuroinflammation and synaptic plasticity, including serine/threonine-protein kinase 1(AKT1), mitogen-activated protein kinase 1(MAPK1), and prostaglandin-endoperoxide synthase 2(PTGS2). This study provides a theoretical reference for the clinical application of Yueju Pills in alleviating the depressive symptoms of psychocardiac diseases.
Animals ; Network Pharmacology ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Metabolomics ; Male ; Depression/genetics* ; Humans ; Hippocampus/drug effects* ; Mice, Inbred C57BL ; Signal Transduction/drug effects*

Objective To explore the relationship between levels of vascular endothelial growth factor(VEGF),insulin-like growth factor 1(IGF-1),and transforming growth factor-β1(TGF-β1)in the synovial fluid of children with avascular necrosis of the femoral head(also known as Perthes disease)and the efficacy of postoperative revascularization,aiming to provide a basis for subsequent diagnosis and treatment.Methods A retrospective study was conducted on 262 children with Perthes disease admitted to the Affiliated Hospital of Gansu University of Chinese Medicine from January 2023 to June 2024.Based on postoperative revascularization efficacy,patients were divided into good revascularization group(n=228)and poor revascularization group(n=34).For poor revascularization group,a 1:2 matched case-control design was used to select 68 age-matched children with hip synovitis who underwent hip joint fluid puncture as control group.Additionally,82 children with Perthes disease treated at the hospital from June 2024 to January 2025 were enrolled as a validation cohort for nomogram model verification.The expression levels of VEGF,IGF-1 and TGF-β1 in the synovial fluid of three groups were compared.Confounding biases were controlled through univariate and stratified analyses.Binary logistic regression analysis was used to identify independent factors affecting the revascularization effect.R software was utilized to draw and verify the nomogram model for predicting the postoperative revascularization effect.Results The levels of VEGF,IGF-1 and TGF-β1 in the synovial fluid of children in poor revascularization group were all higher than those in control group and good revascularization group(P<0.05).After three types of reconstructive surgeries,the levels of VEGF,IGF-1 and TGF-β1 in the synovial fluid of children with poor revascularization were all higher than those in children with good revascularization(P<0.05);however,there was no statistically significant difference in the above indicators among different surgical types(P>0.05).Binary logistic regression analysis showed that the levels of VEGF,IGF-1,and TGF-β1 in the synovial fluid were independent risk factors for poor postoperative revascularization in children with Perthes disease.The area under the ROC curve of the nomogram model established accordingly for predicting poor postoperative revascularization in children with Perthes disease was 0.875(95%CI 0.805-0.945),with a sensitivity of 0.874 and a specificity of 0.851.Moreover,the calibration curve and decision curve analysis(DCA)indicated that the model had good clinical applicability.Conclusions The increased levels of VEGF,IGF-1 and TGF-β1 in synovial fluid are associated with poor postoperative revascularization in children with Perthes disease.These three factors are expected to become prognostic indicators for children with Perthes disease.

Aim To explore the mechanism of Lycium barbarum glycopeptide(LbGP)improving aging in rat primary ovarian granulosa cells.Methods This study divided the cells into a normal group,a DOX group,and four different LbGP concentration treatment groups post-DOX intervention.Results Cell proliferation was assessed using CCK-8,EDU,and Ki67 assays,while aging markers and mitochondrial function-related fac-tors were detected using immunofluorescence and West-ern blotting.The results showed that,compared to the DOX group,LbGP treatment significantly increased cell viability(P＜0.05)and promoted proliferation(P＜0.05).Post LbGP treatment,the β-galactosidase-posi-tive area in cells was significantly reduced compared to the DOX group(P＜0.05).Immunofluorescence re-sults indicated that,compared to the DOX group,levels of p21 and γH2AX significantly decreased(P＜0.05),while pRB increased(P＜0.05)after LbGP treatment.Western blot results showed that,compared to the DOX group,the aging phenotype proteins p21 and p53 significantly decreased(P＜0.05),and pRB notably increased(P＜0.05)in the LbGP treatment group.The release of cytC into the cytoplasm and the activated caspase-9 significantly decreased(P＜0.05);levels of CAMKK2,pAMPK,and mitochondrial calcium homeostasis regulator MCU increased(P＜0.05);nuclear energy metabolism-related proteins SirT1,PGC1α/β and ATP5A1 significantly increased(P＜0.05);compared to the DOX group,ROS levels significantly decreased after LbGP treatment(P＜0.05).Conclusions The results suggest that LbGP can ameliorate DOX-induced aging in rat primary ovar-ian granulosa cells,potentially through the upregulation of the CAMKKβ/AMPK signaling pathway,thereby im-proving mitochondrial calcium homeostasis and increas-ing the expression levels of cell energy metabolism-re-lated regulatory proteins.This provides an experimen-tal basis for LbGP's potential role in supporting the im-provement of ovarian function.

Aim To explore the mechanism of Lycium barbarum glycopeptide(LbGP)improving aging in rat primary ovarian granulosa cells.Methods This study divided the cells into a normal group,a DOX group,and four different LbGP concentration treatment groups post-DOX intervention.Results Cell proliferation was assessed using CCK-8,EDU,and Ki67 assays,while aging markers and mitochondrial function-related fac-tors were detected using immunofluorescence and West-ern blotting.The results showed that,compared to the DOX group,LbGP treatment significantly increased cell viability(P＜0.05)and promoted proliferation(P＜0.05).Post LbGP treatment,the β-galactosidase-posi-tive area in cells was significantly reduced compared to the DOX group(P＜0.05).Immunofluorescence re-sults indicated that,compared to the DOX group,levels of p21 and γH2AX significantly decreased(P＜0.05),while pRB increased(P＜0.05)after LbGP treatment.Western blot results showed that,compared to the DOX group,the aging phenotype proteins p21 and p53 significantly decreased(P＜0.05),and pRB notably increased(P＜0.05)in the LbGP treatment group.The release of cytC into the cytoplasm and the activated caspase-9 significantly decreased(P＜0.05);levels of CAMKK2,pAMPK,and mitochondrial calcium homeostasis regulator MCU increased(P＜0.05);nuclear energy metabolism-related proteins SirT1,PGC1α/β and ATP5A1 significantly increased(P＜0.05);compared to the DOX group,ROS levels significantly decreased after LbGP treatment(P＜0.05).Conclusions The results suggest that LbGP can ameliorate DOX-induced aging in rat primary ovar-ian granulosa cells,potentially through the upregulation of the CAMKKβ/AMPK signaling pathway,thereby im-proving mitochondrial calcium homeostasis and increas-ing the expression levels of cell energy metabolism-re-lated regulatory proteins.This provides an experimen-tal basis for LbGP's potential role in supporting the im-provement of ovarian function.

The growth of three plague phages from Qinghai Plateau in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,PTB5,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were detected through a micromethod based on the OmniLogTM microbial identification system and by the drop method,to provide a scientific basis for future ecological studies and classification based on the host range.For plague vaccine strains EV76 and 614F,successful phage infection and subsequent phage growth were observed in the host bacte-rium.Diminished bacterial growth and respiration and a concomitant decrease in color were observed with the OmniLogTM mi-crobial identification system at 33 ℃ for 48 h.Yersinia pseudotuberculosis PTB5 was sensitive to Yersinia pestis phage 476,but Yersinia pseudotuberculosis PST5 was insensitive to phage 087 and 072204.Three strains of non-Yersinia pestis(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were insensitive to Yersinia pestis pha-ges 087,072204,and 476 showed similar growth curves.The growth of phages 476 and 087,as determined with the drop method,in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersin-ia enterocolitica 52302-2)showed the same results at 37 ℃,on the basis of comparisons with the OmniLogTM microbial i-dentification system;in contrast,phages 072204 did not show plaques on solid medium at 37 ℃ with plague vaccine strains EV76 and 614F.Determination based on the OmniLogTM detection system can be used as an alternative to the traditional determination of the host range,thus providing favorable application val-ue for determining the interaction between the phage and host bacteria.

Damarane-type triterpene saponins are the main active ingredients in Gynostemma pentaphyllum (Thunb.) Makino. By using D101 macroporous adsorption resin and silica gel open-columns, C18 medium-pressure column chromatography, and preparative high performance liquid chromatography, we isolated four compounds from the leaves of G. pentaphyllum planted in Guangxi Zhuang Autonomous Region. Their structures were determined by comprehensive analyses of MS, NMR data and circular dichroism spectroscopy and identified as (3β,12β)-dihydroxy-25-peroxyhydrohydrodammarane-20,23-diene-3-O-[β-D-glucopyranosyl(1→2)]-β-D-glucopyranoside (1), (3β,12β,24S)-trihydroxydammarane-20,25-diene-3-O-[β-D-glucopyranosyl(1→2)]-β-D-glucopyranoside (2), (3β,20α)-dihydroxy-24-en-12β,22S-epoxydammarane-3-O-[β-D-glucopyranosyl(1→2)]-β-D-glucopyranoside (3), (3β,12β,20S)-trihydroxydammarane-24-en-3-O-[6-O-acetyl-β-D-glucopyranosyl(1→2)-β-D-glucopyranosyl]-20-O-β-D-xylopyranosyl(1→3)-α-L-rhamnopyranosyl (1→6)-β-D-glucopyranoside (4). Compounds 1-4 are new dammarane-type triterpene saponins.